Lupus Nephritis
Conditions
Brief summary
The purpose of this study is to evaluate (Abatacept) for treatment of lupus nephritis when used on a background of Cellcept (mycophenolate) and prednisone (corticosteroids)
Interventions
BIOLOGICALBMS-188667
DRUGMycophenolate mofetil
DRUGPrednisone
BIOLOGICALPlacebo matching with BMS-188667
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For additional information please contact the BMS Lupus Nephritis Clinical Trial Matching Service at 855-56-LUPUS. Please visit www.BMSStudyConnect.com for more information on clinical trial participation. Note: Subjects \> 16 are eligible for enrollment at selected centers Inclusion Criteria: * Potential subjects must have active lupus nephritis * Biopsy within 12 months prior to screening visit indicating active Class 3 or 4 proliferative lupus glomerulonephritis (lupus effecting your kidney) * Urine protein creatinine ratio (UPCR) ≥ 1 at Screening * Serum creatinine ≤ 3 mg/dL (ie, ≤ 265 micromol/L) * There must also be evidence of active disease within 3 months of Screening, based on at least one of the following: * Worsening of lupus nephritis OR * UPCR ≥ 3 at Screening OR * Active urine sediment OR * Biopsy within 3 months prior to screening visit indicating active Class 3 or Class 4 active proliferative lupus glomerulonephritis Inclusion Criteria for the Long-Term Extension Period: * Signed Written Informed Consent * Subjects who achieve a complete or partial renal response after completing 2 years of double-blind treatment
Exclusion criteria
* Systemic Lupus Erythematosus (SLE) must be the primary/main autoimmune diagnosis * Current symptoms of severe, progressive, or uncontrolled non-SLE related renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, neurological, or cerebral disease, or other concomitant medical conditions that, in the opinion of the Investigator, might place the subject at unacceptable risk for participation in this study * Significant active Central nervous system (CNS) lupus with the exception of fatigue or mild stable cognitive * Subjects who are diagnosed as end-stage renal disease or whose kidney damage is too significant and irreversible
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants in Complete Renal Response (CR) of Lupus Glomerulonephritis at Day 365 of the Double-blind Period | Day 365 | Number of participants achieving CR was divided by the total number of participants in that arm and expressed as a percentage. CR defined as: eGFR is normal or no \<85% of the baseline; eGFR based on mean creatinine value from day 358 and 365. Proteinuria: UPCR\<0.5 mg/mg. Urine sediment: No cellular casts. Corticosteroid dose: Daily dose must be no \>10 mg prednisone or equiv. for at least 28 days prior to assessment. Participants with \>10mg/day prednisone or equivalent for non-renal disease within 28 days prior to day 365 will be imputed as having achieved CR if the following are true: Met all criteria for CR at day 337 and all criteria for CR except corticosteroid dose at day 365; Investigator confirms increase in steroid dose is not related to renal disease. Adjusted odds ratio is estimated from logistic regression model which includes treatment group, baseline ACEi/ARBs use (Yes/No), race (Asian/ Black/Caucasian/Other) and baseline UPCR as a continuous variable. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Mean Change From Baseline in Urine Protein/Creatinine Ratio (UPCR) at Day 365 of the Double-blind Period in Nephrotic Participants | Baseline and Day 365 | Adjusted Mean Change from Baseline in UPCR at Day 365 of the double-blind period in nephrotic participants |
| Adjusted Mean Change From Baseline in UPCR at Day 365 of the Double-blind Period in Overall Population | Day 1 and Day 365 | Adjusted Mean Change from Baseline in Urine protein/creatinine ratio (UPCR) at Day 365 of the double-blind period in the overall population |
| Adjusted Mean Change From Baseline in UPCR Over Time | Day 365; Day 729, includes data up to July 1st 2017 when double-blind therapy ended | A repeated measure mixed model that included the baseline UPCR value, randomization stratification factors, time, and time by treatment interaction as fixed effects and subject as a random effect was used. |
| Adjusted Mean Change From Baseline in Disease Activity as Measured by BILAG 2004 Over Time During Year 1 of the Double-blind Period | Day 1 to Day 365 | Adjusted mean change from baseline in British Isles Lupus Assessment Group (BILAG) score over time during Year 1 of the double-blind period based on a repeated measure mixed model and presented at each visit in the first 12-month of the double-blind period. BILAG index measures disease activity in different organs/systems separately. BILAG score is calculated for each of 9 systems depending on the clinical features present and whether they are new (4 points), worse (3 points), the same (2 points), improving (1 point) or not present (0 points) in the last 4 weeks compared with previously. BILAG A represents the presence of serious features of lupus. BILAG B represents more moderate features of the disease. BILAG C includes only mild symptomatic features. BILAG D represents prior activity with no current symptoms due to active lupus. BILAG E represents an organ that has never been involved. Overall BILAG score ranges from 0-108, with higher scores reflecting a worse outcome. |
| Number of Participants With Any Adverse Events (AEs) During Year 1 of the Double-blind Period | From Day 1 up to 56 days post last dose in Year 1 of the double-blind period | All AEs were coded and grouped into preferred terms (PT) by system organ class (SOC), using the Medical Dictionary for Regulatory Activities (MedDRA, version 21.0). Investigators determined the intensity of each AE as mild, moderate, severe, or very severe and assessed the relationship to study drug. |
| Percentage of Participants With Ranked Outcome of Complete Renal Response, Partial Renal Response (PR), and No Renal Response (NR) During the Double-blind Period | Day 365, Day 729 | Complete Renal Response or Complete Response (CR): defined as meeting ALL of the following criteria: eGFR normal OR no less than 85% of the baseline value; UPCR \< 0.5; Urine sediment: No cellular casts; Daily corticosteroid dose must be no greater than 10 mg prednisone or equivalent for at least 28 days prior to assessment. Partial Renal Response or Partial Response (PR): defined as meeting ALL of the following criteria: Participant does not meet criteria for CR; eGFR no less than 85% of the lesser of the values at screening or randomization (Day 1); UPCR \< 0.5 OR 50% reduced from baseline and \< 1 if baseline value was \< 3, OR 50% reduced from baseline and \< 3 if baseline value was greater than or equal to 3; Urine sediment: no cellular casts; daily corticosteroid dose no greater than 10 mg/day prednisone or prednisone equivalent for at least 28 days prior to assessment. No Renal Response or No Response (NR): defined as not meeting criteria for CR or PR or withdrawn |
| Median Percent Change From Baseline in UPCR Over Time | Day 365, Day 729 | A repeated measure mixed model that included the baseline UPCR value, randomization stratification factors, time, and time by treatment interaction as fixed effects and subject as a random effect was used. % Change from Baseline = (post baseline - baseline value) / baseline value x 100 |
| Median Time to Complete Renal Response During the Double-blind Period in All Participants | Day 365, Day 729 | The estimate of median time to Complete Renal Response is based on Kaplan-Meier analysis. Complete renal response (CR): defined as meeting ALL of the following criteria: eGFR normal OR no less than 85% of the baseline value; Urine protein/creatinine ratio (UPCR) \< 0.5; Urine sediment: No cellular casts; Daily corticosteroid dose must be no greater than 10 mg prednisone or equivalent for at least 28 days prior to assessment. |
| Median Time to Complete Renal Response During the Double-blind Period in Nephrotic Participants | Day 365, Day 729 | The estimate of median time to Complete Renal Response in nephrotic participants is based on Kaplan-Meier analysis. Complete renal response (CR): defined as meeting ALL of the following criteria: eGFR normal OR no less than 85% of the baseline value; Urine protein/creatinine ratio (UPCR) \< 0.5; Urine sediment: No cellular casts; Daily corticosteroid dose must be no greater than 10 mg prednisone or equivalent for at least 28 days prior to assessment. |
| Median Time to Partial Renal Response During the Double-blind Period in All Participants | Day 365, Day 729 | The estimate of median time to Partial Response (PR) is based on Kaplan-Meier analysis. Partial renal response (PR): defined as meeting ALL of the following criteria: Participant does not meet criteria for CR; eGFR no less than 85% of the lesser of the values at screening or randomization (Day 1); UPCR \< 0.5 OR 50% reduced from baseline and \< 1 if baseline value was \< 3, OR 50% reduced from baseline and \< 3 if baseline value was 3; Urine sediment: no cellular casts; daily corticosteroid dose no greater than 10 mg/day prednisone or prednisone equivalent for at least 28 days prior to assessment |
| Median Time to Partial Renal Response During the Double-blind Period in Nephrotic Participants | Day 365, Day 729 | The estimate of median time to Partial Response (PR) in nephrotic participants is based on Kaplan-Meier analysis. Partial renal response (PR): defined as meeting ALL of the following criteria: Participant does not meet criteria for CR; eGFR no less than 85% of the lesser of the values at screening or randomization (Day 1); UPCR \< 0.5 OR 50% reduced from baseline and \< 1 if baseline value was \< 3, OR 50% reduced from baseline and \< 3 if baseline value was 3; Urine sediment: no cellular casts; daily corticosteroid dose no greater than 10 mg/day prednisone or prednisone equivalent for at least 28 days prior to assessment |
| Adjusted Mean Change From Baseline in eGFR Over Time | Day 365, Day 729 | Estimated glomerular filtration rate(eGFR), will be calculated by the CKD-EPI formula shown below.50 eGFR is expressed as mL/min per 1.73m2. For the purpose of this study lower limit of normal eGFR is defined as 90mL/min per 1.73m2 eGFR = 141 X min (Scr/k, 1)α X max (Scr/k, 1)-1.209 X 0.993Age X (1.018 \[if female\]) X (1.159 \[if black\]) Where Scr is serum creatinine (mg/dL), k is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/k or 1, and max indicates the maximum of Scr/k or 1, age in years. |
| Median Time to First Sustained Change to No Response During the Double-blind Period | Day 365, Day 729 | Sustained response defined as response present at 2 consecutive visits approximately 4 weeks apart. No renal response (NR): defined as not meeting criteria for CR or PR or withdrawn The estimate of median time is based on Kaplan-Meier analysis |
| Number of Participants With Sustained Change From Higher Level of Response to no Response During the Double-blind Period | Day 365, Day 729 | Sustained change to no response is defined as going from CR (or PR) to NR and remaining in NR for at least 2 consecutive visits; visits should be approximately 4 weeks apart. This analysis will be based on time from response CR (or PR) to the first visit in which the no response (NR) was achieved and sustained to the next visit. |
| Adjusted Mean Change From Baseline in Disease Activity as Measured by BILAG 2004 Over Time During the Double-blind Period | Day 1 to Day 729; Day 365 to Day 729 | BILAG index measures and reports disease activity in different organs/systems separately. The BILAG score is calculated for each of nine systems depending on the clinical features present and whether they are new (4 points), worse (3 points), the same (2 points), improving (1 point) or not present (0 points) in the last 4 weeks compared with previously. A BILAG A represents the presence of one or more serious features of lupus. A BILAG B represents more moderate features of the disease. A BILAG C includes only mild symptomatic features. A BILAG D represents only prior activity with no current symptoms due to active lupus. A BILAG E represents an organ that has never been involved. Overall BILAG score ranges from 0-108, with higher scores reflecting a worse outcome. |
| Cmin (ug/mL): Trough Level Serum Concentration of Abatacept Prior to the Administration of the IV Infusion | Days 1 to 365 | Trough level serum concentration of abatacept prior to the administration of the IV infusion on Days 1 to 365 |
| Cmax: Maximum Observed Serum Concentration Following Participants Receiving Active Abatacept IV | at 1 hour post Day 1 dose and 30 minutes post Day 337 dose | Cmax: Maximum observed serum concentration following participants receiving active abatacept IV |
| AUC (TAU): Area Under the Serum Concentration Time Curve Over a Dosing Interval | Days 337 to 365 | AUC (TAU): Area under the serum concentration time curve over a dosing interval between Days 337 to 365. |
| Summary Statistics for Systolic Blood Pressure | Day 1 to Day 729 | Summary statistics for systolic blood pressure |
| Summary Statistics for Diastolic Blood Pressure | Day 1 to Day 729 | Summary statistics for diastolic blood pressure |
| Summary Statistics for Heart Rate | Day 1 to Day 729 | Summary statistics for Heart Rate |
| Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (U/L) | Day 729 | Laboratory assessments were analyzed centrally, with the exception of pregnancy testing. Blood draws and urine collections were performed at visits specified in the protocol. Change from Baseline = Post-baseline - Baseline value. |
| Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (g/L) | Day 729 | Laboratory assessments were analyzed centrally, with the exception of pregnancy testing. Blood draws and urine collections were performed at visits specified in the protocol. Change from Baseline = Post-baseline - Baseline value. |
| Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (Percentage of Blood) | Day 729 | Laboratory assessments were analyzed centrally, with the exception of pregnancy testing. Blood draws and urine collections were performed at visits specified in the protocol. Change from Baseline = Post-baseline - Baseline value. |
| Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (Umol/L) | Day 729 | Laboratory assessments were analyzed centrally, with the exception of pregnancy testing. Blood draws and urine collections were performed at visits specified in the protocol. Change from Baseline = Post-baseline - Baseline value. |
| Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (mmol/L) | Day 729 | Laboratory assessments were analyzed centrally, with the exception of pregnancy testing. Blood draws and urine collections were performed at visits specified in the protocol. Change from Baseline = Post-baseline - Baseline value. |
| Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (x10^9 Cells/L) | Day 729 | Laboratory assessments were analyzed centrally, with the exception of pregnancy testing. Blood draws and urine collections were performed at visits specified in the protocol. Change from Baseline = Post-baseline - Baseline value. |
| Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | Day 1 to Day 365; includes data up to 56 days post last dose in year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier | LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value HEMOGLOBIN g/L 4.0 HB \>3 G/DL DECREASE FROM PRE RX HEMATOCRIT vol 6.3 HCT \<0.75X PRE RX ERYTHROCYTES x10\*12 c/L 5.2 RBC \<0.75X PRE RX PLATELET COUNT x10\*9 c/L 5.0 PLAT \<0.67X LLN OR \>1.5X ULN, OR IF PRE RX\<LLN THEN USE 0.5X PRE RX AND \<100,000/MM3 LEUKOCYTES x10\*9 c/L 6.2 WBC \<0.75X LLN OR \>1.25X ULN, OR IF PRE RX\<LLN THEN USE \<0.8X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.2X PRE RX OR \<LLN EOSINOPHILS (ABSOLUTE) x10\*9 c/L 8.3 EOSA IF VALUE \> .750 X10\*3 c/uL BASOPHILS (ABSOLUTE) x10\*9 c/L 8.3 BASOA IF VALUE \> 400/MM3 MONOCYTES (ABSOLUTE) x10\*9 c/L 8.3 MONOA IF VALUE \> 2000/MM3 LYMPHOCYTES (ABSOLUTE) x10\*9 c/L 8.3 LYMPA IF VALUE \< .750 X10\*3 c/uL OR IF VALUE \> 7.50 X10\*3 c/uL N = the number of participants with at least 1 on treatment lab result for each analyte |
| Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | Day 1 to Day 365; includes data up to 56 days post last dose in year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier | LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value ALKALINE PHOSPHATASE (ALP) U/L 5.0 ALP \>2X ULN, OR IF PRE RX\>ULN THEN USE \>3X PRE RX ASPARTATE AMINOTRANSFERASE (AST) U/L 5.0 AST \>3X ULN, OR IF PRE RX\>ULN THEN USE \>4X PRE RX ALANINE AMINOTRANSFERASE (ALT) U/L 5.0 ALT \>3X ULN, OR IF PRE RX\>ULN THEN USE \>4X PRE RX G-GLUTAMYL TRANSFERASE (GGT) U/L 5.0 GGT \>2X ULN, OR IF PRE RX\>ULN THEN USE \>3X PRE RX BILIRUBIN, TOTAL umol/L 5.1 TBILI \>2X ULN, OR IF PRE RX\>ULN THEN USE \>4X PRE RX BILIRUBIN, DIRECT umol/L 5.1 DBILI \>1.5X ULN, OR IF PRE RX\>ULN THEN USE \>2X PRE RX BLOOD UREA NITROGEN mmol/L 5.1 BUN \>2X PRE RX CREATININE umol/L 5.0 CREAT \>1.5X PRE RX N = the number of participants with at least 1 on treatment lab result for each analyte |
| Number of Participants With Marked Electrolyte Laboratory Abnormalities During Year 1 of the Double Blind Period | Day 1 to Day 365; includes data up to 56 days post last dose in year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier | LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value SODIUM, SERUM mmol/L 4.0 NA \<0.95X LLN OR \>1.05X ULN, OR IF PRE RX\<LLN THEN USE \<0.95X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.05X PRE RX OR \<LLN POTASSIUM, SERUM mmol/L 4.1 K \<0.9X LLN OR \>1.1X ULN, OR IF PRE RX\<LLN THEN USE \<0.9X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.1X PRE RX OR \<LLN CHLORIDE, SERUM mmol/L 5.0 CL \<0.9X LLN OR \>1.1X ULN, OR IF PRE RX\<LLN THEN USE \<0.9X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.1X PRE RX OR \<LLN N = the number of participants with at least 1 on treatment lab result for each analyte |
| Number of Participants With Marked Urinalysis Laboratory Abnormalities During Year 1 of the Double Blind Period | Day 1 to Day 365; includes data up to 56 days post last dose in year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier | LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value PROTEIN, URINE Unknown UPRO IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4 GLUCOSE, URINE N/A UGLU IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4 BLOOD, URINE N/A UBLD IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4 RBC, URINE hpf 5.0 URBC IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4 WBC, URINE hpf 5.0 UWBC IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4 |
| Number of Participants With Other Marked Chemistry Laboratory Abnormalities During Year 1 of the Double Blind Period | Day 1 to Day 365; includes data up to 56 days post last dose in year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier | LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value CALCIUM, TOTAL mmol/L 5.2 CA \<0.8X LLN OR \>1.2X ULN, OR IF PRE RX\<LLN THEN USE \<0.75X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.25X PRE RX OR \<LLN PHOSPHORUS, INORGANIC mmol/L 5.2 PHOS \<0.75X LLN OR \>1.25X ULN, OR IF PRE RX\<LLN THEN USE \<0.67X PRE RX OR \>ULN GLUCOSE, SERUM mmol/L 4.1 GLUC \<65 mg/dL, OR \>220 mg/dL PROTEIN, TOTAL g/L 5.0 TPRO \<0.9X LLN OR \>1.1X ULN, OR IF PRE RX\<LLN THEN USE 0.9X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE 1.1X PRE RX OR \<LLN ALBUMIN g/L 3.0 ALB \<0.9X LLN, OR IF PRE RX\<LLN THEN USE \<0.75X PRE RX CHOLESTEROL, TOTAL (TC) mmol/L 5.2 CHOL \>2X PRE R N = the number of participants with at least 1 on treatment lab result for each analyte |
| Number of Participants With Any Adverse Events (AEs) During Year 2 of the Double-blind Period and Long-term Extension | From the first dose in Year 2 of the double-blind period up to 56 days post last dose | All AEs were coded and grouped into preferred terms (PT) by system organ class (SOC), using the Medical Dictionary for Regulatory Activities (MedDRA, version 21.0). Investigators determined the intensity of each AE as mild, moderate, severe, or very severe and assessed the relationship to study drug. |
| Percentage of Participants in Treatment Failure Over Time During the Double-blind Period | Day 365, Day 729 | Lupus treatment failure is defined as any of the following: Death, unless due to physical trauma or violence; Renal Flare; sustained doubling of creatinine from baseline (greater of Screening or Study Day 1 value); initiation of rescue therapy for treatment of active lupus nephritis after Study Week 20. Overall treatment failure is defined as lupus treatment failure plus discontinuation of study drug for any reason except death due to physical trauma or violence, pregnancy or administrative decision by Sponsor. |
| Median Time to First Treatment Failure and Overall Treatment Failure During the Double-blind Period | Day 365, Day 729 | First treatment failure (or Lupus treatment failure) is defined as any of the following: Death, unless due to physical trauma or violence; Renal Flare; sustained doubling of creatinine from baseline (greater of Screening or Study Day 1 value); initiation of rescue therapy for treatment of active lupus nephritis after Study Week 20. Overall treatment failure is defined as lupus treatment failure plus discontinuation of study drug for any reason except death due to physical trauma or violence, pregnancy or administrative decision by Sponsor. The hazard ratio is estimated using the Cox proportional hazards model which includes treatment group, stratification variables (baseline ACEis/ARBs use, RACE) and baseline UPCR. The estimate of median time is based on Kaplan-Meier analysis |
| Percentage of Nephrotic Participants in Complete Renal Response of Lupus Glomerulonephritis at Day 729 of the Double-blind Period | Day 729 | Number of participants achieving CR was divided by total participants in that arm, expressed as a percentage. CR is defined the following criteria: eGFR is normal or no \<85% of the baseline value; eGFR is based on mean creatinine value from day 358 and 365. Proteinuria: UPCR\<0.5 mg/mg. Urine sediment: No cellular casts. Corticosteroid dose: Daily dose must be no \>10 mg prednisone or equivalent for at least 28 days prior. Subjects with \>10mg/day prednisone or equivalent for non-renal disease within 28 days prior to day 365 will be imputed as CR if the following are true: Met all criteria for CR at day 337 and all criteria for CR except corticosteroid dose at day 365; Investigator confirms increase in steroid dose is not related to renal disease. Adjusted odds ratio is estimated from logistic regression model which includes treatment group, baseline ACEi/ARBs use, race and baseline UPCR as a continuous variable. |
| Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | Day 1 to Day 729 | LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value ALKALINE PHOSPHATASE (ALP) U/L 5.0 ALP \>2X ULN, OR IF PRE RX\>ULN THEN USE \>3X PRE RX ASPARTATE AMINOTRANSFERASE (AST) U/L 5.0 AST \>3X ULN, OR IF PRE RX\>ULN THEN USE \>4X PRE RX ALANINE AMINOTRANSFERASE (ALT) U/L 5.0 ALT \>3X ULN, OR IF PRE RX\>ULN THEN USE \>4X PRE RX G-GLUTAMYL TRANSFERASE (GGT) U/L 5.0 GGT \>2X ULN, OR IF PRE RX\>ULN THEN USE \>3X PRE RX BILIRUBIN, TOTAL umol/L 5.1 TBILI \>2X ULN, OR IF PRE RX\>ULN THEN USE \>4X PRE RX BILIRUBIN, DIRECT umol/L 5.1 DBILI \>1.5X ULN, OR IF PRE RX\>ULN THEN USE \>2X PRE RX BLOOD UREA NITROGEN mmol/L 5.1 BUN \>2X PRE RX CREATININE umol/L 5.0 CREAT \>1.5X PRE RX N = the number of participants with at least 1 on treatment lab result for each analyte |
| Percentage of Participants in Overall Population in Complete Renal Response of Lupus Glomerulonephritis at Day 729 of the Double-blind Period | Day 729 | Number of participants achieving CR was divided by total participants in that arm, expressed as a percentage. CR is defined the following criteria: eGFR is normal or no \<85% of the baseline value; eGFR is based on mean creatinine value from day 358 and 365. Proteinuria: UPCR\<0.5 mg/mg. Urine sediment: No cellular casts. Corticosteroid dose: Daily dose must be no \>10 mg prednisone or equivalent for at least 28 days prior. Subjects with \>10mg/day prednisone or equivalent for non-renal disease within 28 days prior to day 365 will be imputed as CR if the following are true: Met all criteria for CR at day 337 and all criteria for CR except corticosteroid dose at day 365; Investigator confirms increase in steroid dose is not related to renal disease. Adjusted odds ratio is estimated from logistic regression model which includes treatment group, baseline ACEi/ARBs use, race and baseline UPCR as a continuous variable. |
| Percentage of Nephrotic Participants in Complete Renal Response of Lupus Glomerulonephritis at Day 365 of the Double-blind Period | Day 365 | Number of participants achieving CR was divided by total participants in that arm, expressed as a percentage. CR is defined the following criteria: eGFR is normal or no \<85% of the baseline value; eGFR is based on mean creatinine value from day 358 and 365. Proteinuria: UPCR\<0.5 mg/mg. Urine sediment: No cellular casts. Corticosteroid dose: Daily dose must be no \>10 mg prednisone or equivalent for at least 28 days prior. Subjects with \>10mg/day prednisone or equivalent for non-renal disease within 28 days prior to day 365 will be imputed as CR if the following are true: Met all criteria for CR at day 337 and all criteria for CR except corticosteroid dose at day 365; Investigator confirms increase in steroid dose is not related to renal disease. Adjusted odds ratio is estimated from logistic regression model which includes treatment group, baseline ACEi/ARBs use, race and baseline UPCR as a continuous variable. |
| Number of Participants With Marked Electrolyte Laboratory Abnormalities in the Double Blind Period | Day 1 to Day 729 | LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value SODIUM, SERUM mmol/L 4.0 NA \<0.95X LLN OR \>1.05X ULN, OR IF PRE RX\<LLN THEN USE \<0.95X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.05X PRE RX OR \<LLN POTASSIUM, SERUM mmol/L 4.1 K \<0.9X LLN OR \>1.1X ULN, OR IF PRE RX\<LLN THEN USE \<0.9X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.1X PRE RX OR \<LLN CHLORIDE, SERUM mmol/L 5.0 CL \<0.9X LLN OR \>1.1X ULN, OR IF PRE RX\<LLN THEN USE \<0.9X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.1X PRE RX OR \<LLN N = the number of participants with at least 1 on treatment lab result for each analyte |
| Number of Participants With Marked Urinalysis Laboratory Abnormalities in the Double Blind Period | Day 1 to Day 729 | LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value PROTEIN, URINE Unknown UPRO IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4 GLUCOSE, URINE N/A UGLU IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4 BLOOD, URINE N/A UBLD IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4 RBC, URINE hpf 5.0 URBC IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4 WBC, URINE hpf 5.0 UWBC IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4 |
| Number of Participants With Other Marked Chemistry Laboratory Abnormalities in the Double Blind Period | Day 1 to Day 729 | LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value CALCIUM, TOTAL mmol/L 5.2 CA \<0.8X LLN OR \>1.2X ULN, OR IF PRE RX\<LLN THEN USE \<0.75X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.25X PRE RX OR \<LLN PHOSPHORUS, INORGANIC mmol/L 5.2 PHOS \<0.75X LLN OR \>1.25X ULN, OR IF PRE RX\<LLN THEN USE \<0.67X PRE RX OR \>ULN GLUCOSE, SERUM mmol/L 4.1 GLUC \<65 mg/dL, OR \>220 mg/dL PROTEIN, TOTAL g/L 5.0 TPRO \<0.9X LLN OR \>1.1X ULN, OR IF PRE RX\<LLN THEN USE 0.9X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE 1.1X PRE RX OR \<LLN ALBUMIN g/L 3.0 ALB \<0.9X LLN, OR IF PRE RX\<LLN THEN USE \<0.75X PRE RX CHOLESTEROL, TOTAL (TC) mmol/L 5.2 CHOL \>2X PRE R N = the number of participants with at least 1 on treatment lab result for each analyte |
| Number of Participants With Abatacept Induced Antibody Response Over Time in the Double-blind Period | Day 365, Day 729 | Participants who experienced a positive antibody response relative to baseline (ECL Assay) |
| Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | Day 1 to Day 729 | LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value HEMOGLOBIN g/L 4.0 HB \>3 G/DL DECREASE FROM PRE RX HEMATOCRIT vol 6.3 HCT \<0.75X PRE RX ERYTHROCYTES x10\*12 c/L 5.2 RBC \<0.75X PRE RX PLATELET COUNT x10\*9 c/L 5.0 PLAT \<0.67X LLN OR \>1.5X ULN, OR IF PRE RX\<LLN THEN USE 0.5X PRE RX AND \<100,000/MM3 LEUKOCYTES x10\*9 c/L 6.2 WBC \<0.75X LLN OR \>1.25X ULN, OR IF PRE RX\<LLN THEN USE \<0.8X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.2X PRE RX OR \<LLN EOSINOPHILS (ABSOLUTE) x10\*9 c/L 8.3 EOSA IF VALUE \> .750 X10\*3 c/uL BASOPHILS (ABSOLUTE) x10\*9 c/L 8.3 BASOA IF VALUE \> 400/MM3 MONOCYTES (ABSOLUTE) x10\*9 c/L 8.3 MONOA IF VALUE \> 2000/MM3 LYMPHOCYTES (ABSOLUTE) x10\*9 c/L 8.3 LYMPA IF VALUE \< .750 X10\*3 c/uL OR IF VALUE \> 7.50 X10\*3 c/uL N = the number of participants with at least 1 on treatment lab result for each analyte |
Countries
Argentina, Australia, Brazil, Canada, Chile, China, Colombia, Czechia, Hong Kong, India, Israel, Italy, Japan, Mexico, Peru, Puerto Rico, Romania, Russia, South Korea, Spain, Taiwan, Turkey (Türkiye), United States
Participant flow
Pre-assignment details
Overall, 695 participants were enrolled; 406 randomized; and 405 received treatment. 289 participants were screen failures and never treated with study medication; 233 were due to no longer meeting study criteria; 19 withdrew consent; 4 due to Adverse Events; 1 due to death; 1 due to poor/non-compliance; 1 was lost to follow up; and 30 were other.
Participants by arm
| Arm | Count |
|---|---|
| Abatacept IV Abatacept 30 mg/kg injection by intravenous on Days 1,15, 29, and 57, followed by a weight-tiered dose approximating 10mg/kg injection by intravenous every 4 weeks, Mycophenolate mofetil 1.5 g tablet by mouth and Prednisone up to 60 mg tablet by mouth Daily for 104 weeks | 202 |
| Placebo IV Placebo matching with Abatacept injection by intravenous on Days 1,15, 29, and 57, followed by every 4 weeks, Mycophenolate mofetil 1.5 g tablet by mouth and Prednisone up to 60 mg tablet by mouth Daily for 104 Weeks | 203 |
| Total | 405 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Long-Term Extension (LTE) Period | Absence of renal response | 0 | 1 |
| Long-Term Extension (LTE) Period | Administrative reason by Sponsor | 27 | 21 |
| Long-Term Extension (LTE) Period | Adverse Event unrelated to study drug | 1 | 0 |
| Long-Term Extension (LTE) Period | Completed Year 2, did not enter LTE | 33 | 38 |
| Long-Term Extension (LTE) Period | Disease progression | 1 | 4 |
| Long-Term Extension (LTE) Period | Investigator decision, study termination | 0 | 1 |
| Long-Term Extension (LTE) Period | Lost to Follow-up | 0 | 1 |
| Long-Term Extension (LTE) Period | Not effective | 0 | 1 |
| Long-Term Extension (LTE) Period | Participant no longer meets criteria | 1 | 0 |
| Long-Term Extension (LTE) Period | Participant request to stop treatment | 1 | 1 |
| Long-Term Extension (LTE) Period | Participant withdrew consent | 1 | 1 |
| Long-Term Extension (LTE) Period | Pregnancy | 1 | 0 |
| Long-Term Extension (LTE) Period | Study drug toxicity | 1 | 0 |
| Long-Term Extension (LTE) Period | Study was terminated | 0 | 1 |
| Year 1 Period | Adverse Event | 20 | 17 |
| Year 1 Period | Antiproteinuric changed/dose increased | 0 | 1 |
| Year 1 Period | Change in Concomitant Medication | 0 | 1 |
| Year 1 Period | Death | 1 | 1 |
| Year 1 Period | Hypersensitivity to the medication | 0 | 1 |
| Year 1 Period | Lack of Efficacy | 11 | 9 |
| Year 1 Period | Lost to Follow-up | 0 | 2 |
| Year 1 Period | Need of use of Prohibited Medications | 1 | 0 |
| Year 1 Period | Not treated- received ACE inhibition | 1 | 0 |
| Year 1 Period | Participant no longer meets criteria | 6 | 2 |
| Year 1 Period | Poor / non-compliance | 0 | 1 |
| Year 1 Period | Pregnancy | 2 | 0 |
| Year 1 Period | Withdrawal by Subject | 6 | 7 |
| Year 2 Period | Administrative reason by Sponsor | 4 | 3 |
| Year 2 Period | Adverse Event | 7 | 6 |
| Year 2 Period | Completed Year 1, did not enter Year 2 | 2 | 1 |
| Year 2 Period | Given cyclophosphamide, corticosteroids | 0 | 1 |
| Year 2 Period | Lack of Efficacy | 4 | 12 |
| Year 2 Period | Lost to Follow-up | 2 | 0 |
| Year 2 Period | Participant no longer meets criteria | 1 | 4 |
| Year 2 Period | Participant request to stop treatment | 4 | 4 |
| Year 2 Period | Participant went to US stopped treatment | 0 | 1 |
| Year 2 Period | Participant withdrew consent | 1 | 5 |
| Year 2 Period | Pregnancy | 1 | 1 |
Baseline characteristics
| Characteristic | Abatacept IV | Placebo IV | Total |
|---|---|---|---|
| Age, Continuous | 33.1 years STANDARD_DEVIATION 10.75 | 33.2 years STANDARD_DEVIATION 10.48 | 33.1 years STANDARD_DEVIATION 10.6 |
| Race/Ethnicity, Customized African American | 15 Participants | 15 Participants | 30 Participants |
| Race/Ethnicity, Customized Asian | 71 Participants | 74 Participants | 145 Participants |
| Race/Ethnicity, Customized Caucasian | 85 Participants | 71 Participants | 156 Participants |
| Race/Ethnicity, Customized Other | 31 Participants | 43 Participants | 74 Participants |
| Sex: Female, Male Female | 182 Participants | 178 Participants | 360 Participants |
| Sex: Female, Male Male | 20 Participants | 25 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 202 | 6 / 203 |
| other Total, other adverse events | 164 / 202 | 179 / 203 |
| serious Total, serious adverse events | 62 / 202 | 58 / 203 |
Outcome results
Primary
Percentage of Participants in Complete Renal Response (CR) of Lupus Glomerulonephritis at Day 365 of the Double-blind Period
Number of participants achieving CR was divided by the total number of participants in that arm and expressed as a percentage. CR defined as: eGFR is normal or no \<85% of the baseline; eGFR based on mean creatinine value from day 358 and 365. Proteinuria: UPCR\<0.5 mg/mg. Urine sediment: No cellular casts. Corticosteroid dose: Daily dose must be no \>10 mg prednisone or equiv. for at least 28 days prior to assessment. Participants with \>10mg/day prednisone or equivalent for non-renal disease within 28 days prior to day 365 will be imputed as having achieved CR if the following are true: Met all criteria for CR at day 337 and all criteria for CR except corticosteroid dose at day 365; Investigator confirms increase in steroid dose is not related to renal disease. Adjusted odds ratio is estimated from logistic regression model which includes treatment group, baseline ACEi/ARBs use (Yes/No), race (Asian/ Black/Caucasian/Other) and baseline UPCR as a continuous variable.
Time frame: Day 365
Population: All randomized and treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abatacept IV | Percentage of Participants in Complete Renal Response (CR) of Lupus Glomerulonephritis at Day 365 of the Double-blind Period | 35.1 Percentage |
| Placebo IV | Percentage of Participants in Complete Renal Response (CR) of Lupus Glomerulonephritis at Day 365 of the Double-blind Period | 33.5 Percentage |
p-value: 0.726495% CI: [0.7077, 1.6421]Stratified logistic regression
Secondary
Adjusted Mean Change From Baseline in Disease Activity as Measured by BILAG 2004 Over Time During the Double-blind Period
BILAG index measures and reports disease activity in different organs/systems separately. The BILAG score is calculated for each of nine systems depending on the clinical features present and whether they are new (4 points), worse (3 points), the same (2 points), improving (1 point) or not present (0 points) in the last 4 weeks compared with previously. A BILAG A represents the presence of one or more serious features of lupus. A BILAG B represents more moderate features of the disease. A BILAG C includes only mild symptomatic features. A BILAG D represents only prior activity with no current symptoms due to active lupus. A BILAG E represents an organ that has never been involved. Overall BILAG score ranges from 0-108, with higher scores reflecting a worse outcome.
Time frame: Day 1 to Day 729; Day 365 to Day 729
Population: All randomized and treated participants with both post-baseline and baseline measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept IV | Adjusted Mean Change From Baseline in Disease Activity as Measured by BILAG 2004 Over Time During the Double-blind Period | Day 1 to Day 729 | -9.31 Scores on a Scale | Standard Error 0.56 |
| Abatacept IV | Adjusted Mean Change From Baseline in Disease Activity as Measured by BILAG 2004 Over Time During the Double-blind Period | Day 365 to Day 729 | -0.95 Scores on a Scale | Standard Error 0.538 |
| Placebo IV | Adjusted Mean Change From Baseline in Disease Activity as Measured by BILAG 2004 Over Time During the Double-blind Period | Day 1 to Day 729 | -8.53 Scores on a Scale | Standard Error 0.56 |
| Placebo IV | Adjusted Mean Change From Baseline in Disease Activity as Measured by BILAG 2004 Over Time During the Double-blind Period | Day 365 to Day 729 | -0.40 Scores on a Scale | Standard Error 0.53 |
Secondary
Adjusted Mean Change From Baseline in Disease Activity as Measured by BILAG 2004 Over Time During Year 1 of the Double-blind Period
Adjusted mean change from baseline in British Isles Lupus Assessment Group (BILAG) score over time during Year 1 of the double-blind period based on a repeated measure mixed model and presented at each visit in the first 12-month of the double-blind period. BILAG index measures disease activity in different organs/systems separately. BILAG score is calculated for each of 9 systems depending on the clinical features present and whether they are new (4 points), worse (3 points), the same (2 points), improving (1 point) or not present (0 points) in the last 4 weeks compared with previously. BILAG A represents the presence of serious features of lupus. BILAG B represents more moderate features of the disease. BILAG C includes only mild symptomatic features. BILAG D represents prior activity with no current symptoms due to active lupus. BILAG E represents an organ that has never been involved. Overall BILAG score ranges from 0-108, with higher scores reflecting a worse outcome.
Time frame: Day 1 to Day 365
Population: All randomized and treated participants with both post-baseline and baseline measurements
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Abatacept IV | Adjusted Mean Change From Baseline in Disease Activity as Measured by BILAG 2004 Over Time During Year 1 of the Double-blind Period | -8.22 Scores on a Scale |
| Placebo IV | Adjusted Mean Change From Baseline in Disease Activity as Measured by BILAG 2004 Over Time During Year 1 of the Double-blind Period | -7.60 Scores on a Scale |
Secondary
Adjusted Mean Change From Baseline in eGFR Over Time
Estimated glomerular filtration rate(eGFR), will be calculated by the CKD-EPI formula shown below.50 eGFR is expressed as mL/min per 1.73m2. For the purpose of this study lower limit of normal eGFR is defined as 90mL/min per 1.73m2 eGFR = 141 X min (Scr/k, 1)α X max (Scr/k, 1)-1.209 X 0.993Age X (1.018 \[if female\]) X (1.159 \[if black\]) Where Scr is serum creatinine (mg/dL), k is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/k or 1, and max indicates the maximum of Scr/k or 1, age in years.
Time frame: Day 365, Day 729
Population: All randomized and treated participants with both post-baseline and baseline measurements
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Abatacept IV | Adjusted Mean Change From Baseline in eGFR Over Time | Day 365 | 6.85 mL/min per 1.73m2 |
| Abatacept IV | Adjusted Mean Change From Baseline in eGFR Over Time | Day 729 | 7.20 mL/min per 1.73m2 |
| Placebo IV | Adjusted Mean Change From Baseline in eGFR Over Time | Day 365 | 5.85 mL/min per 1.73m2 |
| Placebo IV | Adjusted Mean Change From Baseline in eGFR Over Time | Day 729 | 7.91 mL/min per 1.73m2 |
Secondary
Adjusted Mean Change From Baseline in UPCR at Day 365 of the Double-blind Period in Overall Population
Adjusted Mean Change from Baseline in Urine protein/creatinine ratio (UPCR) at Day 365 of the double-blind period in the overall population
Time frame: Day 1 and Day 365
Population: All randomized and treated participants with both post-baseline and baseline measurements
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abatacept IV | Adjusted Mean Change From Baseline in UPCR at Day 365 of the Double-blind Period in Overall Population | -2.99 UPCR (mg/mg) | Standard Error 0.17 |
| Placebo IV | Adjusted Mean Change From Baseline in UPCR at Day 365 of the Double-blind Period in Overall Population | -2.90 UPCR (mg/mg) | Standard Error 0.16 |
p-value: 0.56195% CI: [-0.41, 0.22]Mixed Models Analysis
Secondary
Adjusted Mean Change From Baseline in UPCR Over Time
A repeated measure mixed model that included the baseline UPCR value, randomization stratification factors, time, and time by treatment interaction as fixed effects and subject as a random effect was used.
Time frame: Day 365; Day 729, includes data up to July 1st 2017 when double-blind therapy ended
Population: All randomized and treated participants with both post-baseline and baseline measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept IV | Adjusted Mean Change From Baseline in UPCR Over Time | Day 365 | -2.95 UPCR (mg/mg) | Standard Error 0.17 |
| Abatacept IV | Adjusted Mean Change From Baseline in UPCR Over Time | Day 729 | -3.13 UPCR (mg/mg) | Standard Error 0.18 |
| Placebo IV | Adjusted Mean Change From Baseline in UPCR Over Time | Day 365 | -2.68 UPCR (mg/mg) | Standard Error 0.17 |
| Placebo IV | Adjusted Mean Change From Baseline in UPCR Over Time | Day 729 | -2.72 UPCR (mg/mg) | Standard Error 0.18 |
Secondary
Adjusted Mean Change From Baseline in Urine Protein/Creatinine Ratio (UPCR) at Day 365 of the Double-blind Period in Nephrotic Participants
Adjusted Mean Change from Baseline in UPCR at Day 365 of the double-blind period in nephrotic participants
Time frame: Baseline and Day 365
Population: All randomized and treated nephrotic participants with both post-baseline and baseline measurements
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abatacept IV | Adjusted Mean Change From Baseline in Urine Protein/Creatinine Ratio (UPCR) at Day 365 of the Double-blind Period in Nephrotic Participants | -5.01 UPCR (mg/mg) | Standard Error 0.33 |
| Placebo IV | Adjusted Mean Change From Baseline in Urine Protein/Creatinine Ratio (UPCR) at Day 365 of the Double-blind Period in Nephrotic Participants | -4.84 UPCR (mg/mg) | Standard Error 0.35 |
p-value: 0.57195% CI: [-0.76, 0.42]Mixed Models Analysis
Secondary
AUC (TAU): Area Under the Serum Concentration Time Curve Over a Dosing Interval
AUC (TAU): Area under the serum concentration time curve over a dosing interval between Days 337 to 365.
Time frame: Days 337 to 365
Population: All participants who received at least 1 Abatacept Infusion and have at least 1 Cmin value during Year 1 of the double-blind period
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Abatacept IV | AUC (TAU): Area Under the Serum Concentration Time Curve Over a Dosing Interval | 36480.24 ug*h/mL | Geometric Coefficient of Variation 29.2 |
Secondary
Cmax: Maximum Observed Serum Concentration Following Participants Receiving Active Abatacept IV
Cmax: Maximum observed serum concentration following participants receiving active abatacept IV
Time frame: at 1 hour post Day 1 dose and 30 minutes post Day 337 dose
Population: All participants who received at least 1 Abatacept Infusion and have at least 1 Cmin value during Year 1 of the double-blind period
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept IV | Cmax: Maximum Observed Serum Concentration Following Participants Receiving Active Abatacept IV | Day 1 | 527.43 ug/mL | Geometric Coefficient of Variation 59.6 |
| Abatacept IV | Cmax: Maximum Observed Serum Concentration Following Participants Receiving Active Abatacept IV | Day 337 | 203.51 ug/mL | Geometric Coefficient of Variation 30.6 |
Secondary
Cmin (ug/mL): Trough Level Serum Concentration of Abatacept Prior to the Administration of the IV Infusion
Trough level serum concentration of abatacept prior to the administration of the IV infusion on Days 1 to 365
Time frame: Days 1 to 365
Population: All participants who received at least 1 Abatacept Infusion and have at least 1 Cmin value during Year 1 of the double-blind period.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept IV | Cmin (ug/mL): Trough Level Serum Concentration of Abatacept Prior to the Administration of the IV Infusion | Day 15 | 69.97 ug/mL | Geometric Coefficient of Variation 91.4 |
| Abatacept IV | Cmin (ug/mL): Trough Level Serum Concentration of Abatacept Prior to the Administration of the IV Infusion | Day 29 | 90.46 ug/mL | Geometric Coefficient of Variation 56.8 |
| Abatacept IV | Cmin (ug/mL): Trough Level Serum Concentration of Abatacept Prior to the Administration of the IV Infusion | Day 57 | 36.43 ug/mL | Geometric Coefficient of Variation 84.4 |
| Abatacept IV | Cmin (ug/mL): Trough Level Serum Concentration of Abatacept Prior to the Administration of the IV Infusion | Day 85 | 34.46 ug/mL | Geometric Coefficient of Variation 55.4 |
| Abatacept IV | Cmin (ug/mL): Trough Level Serum Concentration of Abatacept Prior to the Administration of the IV Infusion | Day 113 | 16.42 ug/mL | Geometric Coefficient of Variation 69.2 |
| Abatacept IV | Cmin (ug/mL): Trough Level Serum Concentration of Abatacept Prior to the Administration of the IV Infusion | Day 169 | 13.98 ug/mL | Geometric Coefficient of Variation 64.5 |
| Abatacept IV | Cmin (ug/mL): Trough Level Serum Concentration of Abatacept Prior to the Administration of the IV Infusion | Day 281 | 14.44 ug/mL | Geometric Coefficient of Variation 54.7 |
| Abatacept IV | Cmin (ug/mL): Trough Level Serum Concentration of Abatacept Prior to the Administration of the IV Infusion | Day 337 | 14.99 ug/mL | Geometric Coefficient of Variation 73.6 |
| Abatacept IV | Cmin (ug/mL): Trough Level Serum Concentration of Abatacept Prior to the Administration of the IV Infusion | Day 365 | 13.62 ug/mL | Geometric Coefficient of Variation 51.7 |
Secondary
Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (g/L)
Laboratory assessments were analyzed centrally, with the exception of pregnancy testing. Blood draws and urine collections were performed at visits specified in the protocol. Change from Baseline = Post-baseline - Baseline value.
Time frame: Day 729
Population: All treated participants with both post-baseline and baseline measurements
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Abatacept IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (g/L) | ALBUMIN (g/L) | 9.2 g/L |
| Abatacept IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (g/L) | HEMOGLOBIN (g/L) | 8.8 g/L |
| Abatacept IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (g/L) | PROTEIN, TOTAL (g/L) | 9.9 g/L |
| Placebo IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (g/L) | PROTEIN, TOTAL (g/L) | 10.1 g/L |
| Placebo IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (g/L) | ALBUMIN (g/L) | 8.1 g/L |
| Placebo IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (g/L) | HEMOGLOBIN (g/L) | 9.0 g/L |
Secondary
Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (mmol/L)
Laboratory assessments were analyzed centrally, with the exception of pregnancy testing. Blood draws and urine collections were performed at visits specified in the protocol. Change from Baseline = Post-baseline - Baseline value.
Time frame: Day 729
Population: All treated participants with both post-baseline and baseline measurements
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Abatacept IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (mmol/L) | CHLORIDE, SERUM (mmol/L) | -1.1 mmol/L |
| Abatacept IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (mmol/L) | PHOSPHORUS, INORGANIC (mmol/L) | -0.077 mmol/L |
| Abatacept IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (mmol/L) | CALCIUM, TOTAL (mmol/L) | 0.097 mmol/L |
| Abatacept IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (mmol/L) | POTASSIUM, SERUM (mmol/L) | -0.02 mmol/L |
| Abatacept IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (mmol/L) | GLUCOSE, SERUM (mmol/L) | -0.23 mmol/L |
| Abatacept IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (mmol/L) | SODIUM, SERUM (mmol/L) | -0.2 mmol/L |
| Abatacept IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (mmol/L) | BLOOD UREA NITROGEN (mmol/L) | -2.31 mmol/L |
| Placebo IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (mmol/L) | SODIUM, SERUM (mmol/L) | -0.5 mmol/L |
| Placebo IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (mmol/L) | BLOOD UREA NITROGEN (mmol/L) | -2.25 mmol/L |
| Placebo IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (mmol/L) | CALCIUM, TOTAL (mmol/L) | 0.108 mmol/L |
| Placebo IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (mmol/L) | CHLORIDE, SERUM (mmol/L) | -0.5 mmol/L |
| Placebo IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (mmol/L) | GLUCOSE, SERUM (mmol/L) | -0.58 mmol/L |
| Placebo IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (mmol/L) | PHOSPHORUS, INORGANIC (mmol/L) | -0.037 mmol/L |
| Placebo IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (mmol/L) | POTASSIUM, SERUM (mmol/L) | -0.10 mmol/L |
Secondary
Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (Percentage of Blood)
Laboratory assessments were analyzed centrally, with the exception of pregnancy testing. Blood draws and urine collections were performed at visits specified in the protocol. Change from Baseline = Post-baseline - Baseline value.
Time frame: Day 729
Population: All treated participants with both post-baseline and baseline measurements
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Abatacept IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (Percentage of Blood) | 0.0328 Percentage |
| Placebo IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (Percentage of Blood) | 0.0325 Percentage |
Secondary
Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (U/L)
Laboratory assessments were analyzed centrally, with the exception of pregnancy testing. Blood draws and urine collections were performed at visits specified in the protocol. Change from Baseline = Post-baseline - Baseline value.
Time frame: Day 729
Population: All treated participants with both post-baseline and baseline measurements
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Abatacept IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (U/L) | ALKALINE PHOSPHATASE (ALP) (U/L) | 8.2 U/L |
| Abatacept IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (U/L) | ALANINE AMINOTRANSFERASE (ALT) (U/L) | -2.2 U/L |
| Abatacept IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (U/L) | ASPARTATE AMINOTRANSFERASE (AST) (U/L) | 0.3 U/L |
| Abatacept IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (U/L) | G-GLUTAMYL TRANSFERASE (GGT) (U/L) | -5.3 U/L |
| Placebo IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (U/L) | G-GLUTAMYL TRANSFERASE (GGT) (U/L) | -4.1 U/L |
| Placebo IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (U/L) | ALANINE AMINOTRANSFERASE (ALT) (U/L) | -3.4 U/L |
| Placebo IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (U/L) | ALKALINE PHOSPHATASE (ALP) (U/L) | 11.7 U/L |
| Placebo IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (U/L) | ASPARTATE AMINOTRANSFERASE (AST) (U/L) | 0.3 U/L |
Secondary
Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (Umol/L)
Laboratory assessments were analyzed centrally, with the exception of pregnancy testing. Blood draws and urine collections were performed at visits specified in the protocol. Change from Baseline = Post-baseline - Baseline value.
Time frame: Day 729
Population: All treated participants with both post-baseline and baseline measurements
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Abatacept IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (Umol/L) | BILIRUBIN, TOTAL (umol/L) | 1.77 umol/L |
| Abatacept IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (Umol/L) | CREATININE (umol/L) | -5.6 umol/L |
| Placebo IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (Umol/L) | BILIRUBIN, TOTAL (umol/L) | 1.00 umol/L |
| Placebo IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (Umol/L) | CREATININE (umol/L) | -6.2 umol/L |
Secondary
Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (x10^9 Cells/L)
Laboratory assessments were analyzed centrally, with the exception of pregnancy testing. Blood draws and urine collections were performed at visits specified in the protocol. Change from Baseline = Post-baseline - Baseline value.
Time frame: Day 729
Population: All treated participants with both post-baseline and baseline measurements
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Abatacept IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (x10^9 Cells/L) | EOSINOPHILS (ABSOLUTE) (x10^9 cells/L) | 0.034 x10^9 cells/L |
| Abatacept IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (x10^9 Cells/L) | NEUTROPHILS (ABSOLUTE) (x10^9 cells/L) | -2.259 x10^9 cells/L |
| Abatacept IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (x10^9 Cells/L) | LYMPHOCYTES (ABSOLUTE) (x10^9 cells/L) | 0.141 x10^9 cells/L |
| Abatacept IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (x10^9 Cells/L) | PLATELET COUNT (x10^9 cells/L) | -4.9 x10^9 cells/L |
| Abatacept IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (x10^9 Cells/L) | MONOCYTES (ABSOLUTE) (x10^9 cells/L) | -0.018 x10^9 cells/L |
| Placebo IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (x10^9 Cells/L) | PLATELET COUNT (x10^9 cells/L) | -9.1 x10^9 cells/L |
| Placebo IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (x10^9 Cells/L) | EOSINOPHILS (ABSOLUTE) (x10^9 cells/L) | 0.010 x10^9 cells/L |
| Placebo IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (x10^9 Cells/L) | MONOCYTES (ABSOLUTE) (x10^9 cells/L) | -0.050 x10^9 cells/L |
| Placebo IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (x10^9 Cells/L) | NEUTROPHILS (ABSOLUTE) (x10^9 cells/L) | -2.289 x10^9 cells/L |
| Placebo IV | Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (x10^9 Cells/L) | LYMPHOCYTES (ABSOLUTE) (x10^9 cells/L) | -0.149 x10^9 cells/L |
Secondary
Median Percent Change From Baseline in UPCR Over Time
A repeated measure mixed model that included the baseline UPCR value, randomization stratification factors, time, and time by treatment interaction as fixed effects and subject as a random effect was used. % Change from Baseline = (post baseline - baseline value) / baseline value x 100
Time frame: Day 365, Day 729
Population: All randomized and treated participants with both post-baseline and baseline measurements
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Abatacept IV | Median Percent Change From Baseline in UPCR Over Time | Day 365 | -83.77 Percent |
| Abatacept IV | Median Percent Change From Baseline in UPCR Over Time | Day 729 | -89.83 Percent |
| Placebo IV | Median Percent Change From Baseline in UPCR Over Time | Day 365 | -84.12 Percent |
| Placebo IV | Median Percent Change From Baseline in UPCR Over Time | Day 729 | -87.28 Percent |
Secondary
Median Time to Complete Renal Response During the Double-blind Period in All Participants
The estimate of median time to Complete Renal Response is based on Kaplan-Meier analysis. Complete renal response (CR): defined as meeting ALL of the following criteria: eGFR normal OR no less than 85% of the baseline value; Urine protein/creatinine ratio (UPCR) \< 0.5; Urine sediment: No cellular casts; Daily corticosteroid dose must be no greater than 10 mg prednisone or equivalent for at least 28 days prior to assessment.
Time frame: Day 365, Day 729
Population: All randomized and treated participants, as observed, calculated per modified criteria (UPCR and eGFR only)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Abatacept IV | Median Time to Complete Renal Response During the Double-blind Period in All Participants | Day 365 | 280.0 Days |
| Abatacept IV | Median Time to Complete Renal Response During the Double-blind Period in All Participants | Day 729 | 170.0 Days |
| Placebo IV | Median Time to Complete Renal Response During the Double-blind Period in All Participants | Day 365 | 309.0 Days |
| Placebo IV | Median Time to Complete Renal Response During the Double-blind Period in All Participants | Day 729 | 282.0 Days |
Secondary
Median Time to Complete Renal Response During the Double-blind Period in Nephrotic Participants
The estimate of median time to Complete Renal Response in nephrotic participants is based on Kaplan-Meier analysis. Complete renal response (CR): defined as meeting ALL of the following criteria: eGFR normal OR no less than 85% of the baseline value; Urine protein/creatinine ratio (UPCR) \< 0.5; Urine sediment: No cellular casts; Daily corticosteroid dose must be no greater than 10 mg prednisone or equivalent for at least 28 days prior to assessment.
Time frame: Day 365, Day 729
Population: All randomized and treated nephrotic participants, as observed, calculated per modified criteria (UPCR and eGFR only); Nephrotic is defined as screening UPCR \>= 3.0 mg/mg (\>=339mg/mmol)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Abatacept IV | Median Time to Complete Renal Response During the Double-blind Period in Nephrotic Participants | Day 729 | 365.0 Days |
| Abatacept IV | Median Time to Complete Renal Response During the Double-blind Period in Nephrotic Participants | Day 365 | 366.0 Days |
| Placebo IV | Median Time to Complete Renal Response During the Double-blind Period in Nephrotic Participants | Day 365 | 368.0 Days |
| Placebo IV | Median Time to Complete Renal Response During the Double-blind Period in Nephrotic Participants | Day 729 | 368.0 Days |
Secondary
Median Time to First Sustained Change to No Response During the Double-blind Period
Sustained response defined as response present at 2 consecutive visits approximately 4 weeks apart. No renal response (NR): defined as not meeting criteria for CR or PR or withdrawn The estimate of median time is based on Kaplan-Meier analysis
Time frame: Day 365, Day 729
Population: All randomized and treated participants
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Abatacept IV | Median Time to First Sustained Change to No Response During the Double-blind Period | Day 365 | NA Days |
| Abatacept IV | Median Time to First Sustained Change to No Response During the Double-blind Period | Day 729 | NA Days |
| Placebo IV | Median Time to First Sustained Change to No Response During the Double-blind Period | Day 365 | NA Days |
| Placebo IV | Median Time to First Sustained Change to No Response During the Double-blind Period | Day 729 | NA Days |
Secondary
Median Time to First Treatment Failure and Overall Treatment Failure During the Double-blind Period
First treatment failure (or Lupus treatment failure) is defined as any of the following: Death, unless due to physical trauma or violence; Renal Flare; sustained doubling of creatinine from baseline (greater of Screening or Study Day 1 value); initiation of rescue therapy for treatment of active lupus nephritis after Study Week 20. Overall treatment failure is defined as lupus treatment failure plus discontinuation of study drug for any reason except death due to physical trauma or violence, pregnancy or administrative decision by Sponsor. The hazard ratio is estimated using the Cox proportional hazards model which includes treatment group, stratification variables (baseline ACEis/ARBs use, RACE) and baseline UPCR. The estimate of median time is based on Kaplan-Meier analysis
Time frame: Day 365, Day 729
Population: All randomized and treated participants
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Abatacept IV | Median Time to First Treatment Failure and Overall Treatment Failure During the Double-blind Period | First treatment failure (FTF) - Day 365 | NA Days |
| Abatacept IV | Median Time to First Treatment Failure and Overall Treatment Failure During the Double-blind Period | Overall treatment failure (OTF) - Day 365 | NA Days |
| Abatacept IV | Median Time to First Treatment Failure and Overall Treatment Failure During the Double-blind Period | FTF - Day 729 | NA Days |
| Abatacept IV | Median Time to First Treatment Failure and Overall Treatment Failure During the Double-blind Period | OTF - Day 729 | NA Days |
| Placebo IV | Median Time to First Treatment Failure and Overall Treatment Failure During the Double-blind Period | OTF - Day 729 | NA Days |
| Placebo IV | Median Time to First Treatment Failure and Overall Treatment Failure During the Double-blind Period | First treatment failure (FTF) - Day 365 | NA Days |
| Placebo IV | Median Time to First Treatment Failure and Overall Treatment Failure During the Double-blind Period | FTF - Day 729 | NA Days |
| Placebo IV | Median Time to First Treatment Failure and Overall Treatment Failure During the Double-blind Period | Overall treatment failure (OTF) - Day 365 | NA Days |
Secondary
Median Time to Partial Renal Response During the Double-blind Period in All Participants
The estimate of median time to Partial Response (PR) is based on Kaplan-Meier analysis. Partial renal response (PR): defined as meeting ALL of the following criteria: Participant does not meet criteria for CR; eGFR no less than 85% of the lesser of the values at screening or randomization (Day 1); UPCR \< 0.5 OR 50% reduced from baseline and \< 1 if baseline value was \< 3, OR 50% reduced from baseline and \< 3 if baseline value was 3; Urine sediment: no cellular casts; daily corticosteroid dose no greater than 10 mg/day prednisone or prednisone equivalent for at least 28 days prior to assessment
Time frame: Day 365, Day 729
Population: All randomized and treated participants, as observed, calculated per modified criteria (UPCR and eGFR only)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Abatacept IV | Median Time to Partial Renal Response During the Double-blind Period in All Participants | Day 365 | 226.0 Days |
| Abatacept IV | Median Time to Partial Renal Response During the Double-blind Period in All Participants | Day 729 | 59.0 Days |
| Placebo IV | Median Time to Partial Renal Response During the Double-blind Period in All Participants | Day 365 | 253.0 Days |
| Placebo IV | Median Time to Partial Renal Response During the Double-blind Period in All Participants | Day 729 | 58.0 Days |
Secondary
Median Time to Partial Renal Response During the Double-blind Period in Nephrotic Participants
The estimate of median time to Partial Response (PR) in nephrotic participants is based on Kaplan-Meier analysis. Partial renal response (PR): defined as meeting ALL of the following criteria: Participant does not meet criteria for CR; eGFR no less than 85% of the lesser of the values at screening or randomization (Day 1); UPCR \< 0.5 OR 50% reduced from baseline and \< 1 if baseline value was \< 3, OR 50% reduced from baseline and \< 3 if baseline value was 3; Urine sediment: no cellular casts; daily corticosteroid dose no greater than 10 mg/day prednisone or prednisone equivalent for at least 28 days prior to assessment
Time frame: Day 365, Day 729
Population: All randomized and treated nephrotic participants, as observed, calculated per modified criteria (UPCR and eGFR only); Nephrotic is defined as screening UPCR \>= 3.0 mg/mg (\>=339mg/mmol)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Abatacept IV | Median Time to Partial Renal Response During the Double-blind Period in Nephrotic Participants | Day 365 | 225.0 Days |
| Abatacept IV | Median Time to Partial Renal Response During the Double-blind Period in Nephrotic Participants | Day 729 | 58.5 Days |
| Placebo IV | Median Time to Partial Renal Response During the Double-blind Period in Nephrotic Participants | Day 729 | 56.0 Days |
| Placebo IV | Median Time to Partial Renal Response During the Double-blind Period in Nephrotic Participants | Day 365 | 196.0 Days |
Secondary
Number of Participants With Abatacept Induced Antibody Response Over Time in the Double-blind Period
Participants who experienced a positive antibody response relative to baseline (ECL Assay)
Time frame: Day 365, Day 729
Population: All treated participants in the immunogenicity analysis population for Year 1.~Note: Study terminated, Year 2 data not collected
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept IV | Number of Participants With Abatacept Induced Antibody Response Over Time in the Double-blind Period | Day 365, overall | 7 Participants |
| Placebo IV | Number of Participants With Abatacept Induced Antibody Response Over Time in the Double-blind Period | Day 365, overall | 9 Participants |
Secondary
Number of Participants With Any Adverse Events (AEs) During Year 1 of the Double-blind Period
All AEs were coded and grouped into preferred terms (PT) by system organ class (SOC), using the Medical Dictionary for Regulatory Activities (MedDRA, version 21.0). Investigators determined the intensity of each AE as mild, moderate, severe, or very severe and assessed the relationship to study drug.
Time frame: From Day 1 up to 56 days post last dose in Year 1 of the double-blind period
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept IV | Number of Participants With Any Adverse Events (AEs) During Year 1 of the Double-blind Period | Participants with peri-infusional Adverse Events | 7 Participants |
| Abatacept IV | Number of Participants With Any Adverse Events (AEs) During Year 1 of the Double-blind Period | Participants with Adverse Events | 188 Participants |
| Abatacept IV | Number of Participants With Any Adverse Events (AEs) During Year 1 of the Double-blind Period | Participants with Serious Adverse Events | 49 Participants |
| Abatacept IV | Number of Participants With Any Adverse Events (AEs) During Year 1 of the Double-blind Period | Participants with infection Adverse Events | 150 Participants |
| Abatacept IV | Number of Participants With Any Adverse Events (AEs) During Year 1 of the Double-blind Period | Participants with malignancies | 2 Participants |
| Abatacept IV | Number of Participants With Any Adverse Events (AEs) During Year 1 of the Double-blind Period | Participants with autoimmune events | 10 Participants |
| Abatacept IV | Number of Participants With Any Adverse Events (AEs) During Year 1 of the Double-blind Period | Participants with acute infusional Adverse Events | 2 Participants |
| Placebo IV | Number of Participants With Any Adverse Events (AEs) During Year 1 of the Double-blind Period | Participants with peri-infusional Adverse Events | 9 Participants |
| Placebo IV | Number of Participants With Any Adverse Events (AEs) During Year 1 of the Double-blind Period | Participants with malignancies | 1 Participants |
| Placebo IV | Number of Participants With Any Adverse Events (AEs) During Year 1 of the Double-blind Period | Participants with Adverse Events | 194 Participants |
| Placebo IV | Number of Participants With Any Adverse Events (AEs) During Year 1 of the Double-blind Period | Participants with acute infusional Adverse Events | 4 Participants |
| Placebo IV | Number of Participants With Any Adverse Events (AEs) During Year 1 of the Double-blind Period | Participants with Serious Adverse Events | 39 Participants |
| Placebo IV | Number of Participants With Any Adverse Events (AEs) During Year 1 of the Double-blind Period | Participants with autoimmune events | 9 Participants |
| Placebo IV | Number of Participants With Any Adverse Events (AEs) During Year 1 of the Double-blind Period | Participants with infection Adverse Events | 147 Participants |
Secondary
Number of Participants With Any Adverse Events (AEs) During Year 2 of the Double-blind Period and Long-term Extension
All AEs were coded and grouped into preferred terms (PT) by system organ class (SOC), using the Medical Dictionary for Regulatory Activities (MedDRA, version 21.0). Investigators determined the intensity of each AE as mild, moderate, severe, or very severe and assessed the relationship to study drug.
Time frame: From the first dose in Year 2 of the double-blind period up to 56 days post last dose
Population: All treated participants in Year 2
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept IV | Number of Participants With Any Adverse Events (AEs) During Year 2 of the Double-blind Period and Long-term Extension | Participants with malignancies | 0 Participants |
| Abatacept IV | Number of Participants With Any Adverse Events (AEs) During Year 2 of the Double-blind Period and Long-term Extension | Participants with autoimmune events | 7 Participants |
| Abatacept IV | Number of Participants With Any Adverse Events (AEs) During Year 2 of the Double-blind Period and Long-term Extension | Participants with Adverse Events | 127 Participants |
| Abatacept IV | Number of Participants With Any Adverse Events (AEs) During Year 2 of the Double-blind Period and Long-term Extension | Participants with Serious Adverse Events | 15 Participants |
| Abatacept IV | Number of Participants With Any Adverse Events (AEs) During Year 2 of the Double-blind Period and Long-term Extension | Participants with infection Adverse Events | 100 Participants |
| Placebo IV | Number of Participants With Any Adverse Events (AEs) During Year 2 of the Double-blind Period and Long-term Extension | Participants with infection Adverse Events | 107 Participants |
| Placebo IV | Number of Participants With Any Adverse Events (AEs) During Year 2 of the Double-blind Period and Long-term Extension | Participants with Serious Adverse Events | 25 Participants |
| Placebo IV | Number of Participants With Any Adverse Events (AEs) During Year 2 of the Double-blind Period and Long-term Extension | Participants with autoimmune events | 11 Participants |
| Placebo IV | Number of Participants With Any Adverse Events (AEs) During Year 2 of the Double-blind Period and Long-term Extension | Participants with malignancies | 1 Participants |
| Placebo IV | Number of Participants With Any Adverse Events (AEs) During Year 2 of the Double-blind Period and Long-term Extension | Participants with Adverse Events | 137 Participants |
Secondary
Number of Participants With Marked Electrolyte Laboratory Abnormalities During Year 1 of the Double Blind Period
LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value SODIUM, SERUM mmol/L 4.0 NA \<0.95X LLN OR \>1.05X ULN, OR IF PRE RX\<LLN THEN USE \<0.95X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.05X PRE RX OR \<LLN POTASSIUM, SERUM mmol/L 4.1 K \<0.9X LLN OR \>1.1X ULN, OR IF PRE RX\<LLN THEN USE \<0.9X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.1X PRE RX OR \<LLN CHLORIDE, SERUM mmol/L 5.0 CL \<0.9X LLN OR \>1.1X ULN, OR IF PRE RX\<LLN THEN USE \<0.9X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.1X PRE RX OR \<LLN N = the number of participants with at least 1 on treatment lab result for each analyte
Time frame: Day 1 to Day 365; includes data up to 56 days post last dose in year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities During Year 1 of the Double Blind Period | PHOSPHORUS, INORGANIC, low | 9 participants |
| Abatacept IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities During Year 1 of the Double Blind Period | SODIUM, SERUM, low | 1 participants |
| Abatacept IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities During Year 1 of the Double Blind Period | SODIUM, SERUM, high | 2 participants |
| Abatacept IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities During Year 1 of the Double Blind Period | POTASSIUM, SERUM, low | 3 participants |
| Abatacept IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities During Year 1 of the Double Blind Period | POTASSIUM, SERUM, high | 7 participants |
| Abatacept IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities During Year 1 of the Double Blind Period | CHLORIDE, SERUM, low | 0 participants |
| Abatacept IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities During Year 1 of the Double Blind Period | CHLORIDE, SERUM, high | 0 participants |
| Abatacept IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities During Year 1 of the Double Blind Period | CALCIUM, TOTAL, low | 1 participants |
| Abatacept IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities During Year 1 of the Double Blind Period | CALCIUM, TOTAL, high | 2 participants |
| Abatacept IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities During Year 1 of the Double Blind Period | PHOSPHORUS, INORGANIC, high | 13 participants |
| Placebo IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities During Year 1 of the Double Blind Period | CALCIUM, TOTAL, low | 1 participants |
| Placebo IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities During Year 1 of the Double Blind Period | PHOSPHORUS, INORGANIC, low | 7 participants |
| Placebo IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities During Year 1 of the Double Blind Period | CHLORIDE, SERUM, low | 1 participants |
| Placebo IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities During Year 1 of the Double Blind Period | SODIUM, SERUM, low | 1 participants |
| Placebo IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities During Year 1 of the Double Blind Period | PHOSPHORUS, INORGANIC, high | 13 participants |
| Placebo IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities During Year 1 of the Double Blind Period | SODIUM, SERUM, high | 2 participants |
| Placebo IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities During Year 1 of the Double Blind Period | CHLORIDE, SERUM, high | 0 participants |
| Placebo IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities During Year 1 of the Double Blind Period | POTASSIUM, SERUM, low | 5 participants |
| Placebo IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities During Year 1 of the Double Blind Period | CALCIUM, TOTAL, high | 0 participants |
| Placebo IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities During Year 1 of the Double Blind Period | POTASSIUM, SERUM, high | 7 participants |
Secondary
Number of Participants With Marked Electrolyte Laboratory Abnormalities in the Double Blind Period
LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value SODIUM, SERUM mmol/L 4.0 NA \<0.95X LLN OR \>1.05X ULN, OR IF PRE RX\<LLN THEN USE \<0.95X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.05X PRE RX OR \<LLN POTASSIUM, SERUM mmol/L 4.1 K \<0.9X LLN OR \>1.1X ULN, OR IF PRE RX\<LLN THEN USE \<0.9X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.1X PRE RX OR \<LLN CHLORIDE, SERUM mmol/L 5.0 CL \<0.9X LLN OR \>1.1X ULN, OR IF PRE RX\<LLN THEN USE \<0.9X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.1X PRE RX OR \<LLN N = the number of participants with at least 1 on treatment lab result for each analyte
Time frame: Day 1 to Day 729
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities in the Double Blind Period | POTASSIUM, SERUM, low | 2 participants |
| Abatacept IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities in the Double Blind Period | CHLORIDE, SERUM, high | 0 participants |
| Abatacept IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities in the Double Blind Period | SODIUM, SERUM, high | 0 participants |
| Abatacept IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities in the Double Blind Period | CALCIUM, TOTAL, low | 0 participants |
| Abatacept IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities in the Double Blind Period | POTASSIUM, SERUM, high | 3 participants |
| Abatacept IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities in the Double Blind Period | CALCIUM, TOTAL, high | 1 participants |
| Abatacept IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities in the Double Blind Period | SODIUM, SERUM, low | 0 participants |
| Abatacept IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities in the Double Blind Period | PHOSPHORUS, INORGANIC, low | 3 participants |
| Abatacept IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities in the Double Blind Period | PHOSPHORUS, INORGANIC, high | 6 participants |
| Abatacept IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities in the Double Blind Period | CHLORIDE, SERUM, low | 0 participants |
| Placebo IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities in the Double Blind Period | PHOSPHORUS, INORGANIC, high | 3 participants |
| Placebo IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities in the Double Blind Period | SODIUM, SERUM, low | 0 participants |
| Placebo IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities in the Double Blind Period | SODIUM, SERUM, high | 1 participants |
| Placebo IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities in the Double Blind Period | POTASSIUM, SERUM, low | 2 participants |
| Placebo IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities in the Double Blind Period | POTASSIUM, SERUM, high | 2 participants |
| Placebo IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities in the Double Blind Period | CHLORIDE, SERUM, low | 1 participants |
| Placebo IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities in the Double Blind Period | CHLORIDE, SERUM, high | 0 participants |
| Placebo IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities in the Double Blind Period | CALCIUM, TOTAL, low | 0 participants |
| Placebo IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities in the Double Blind Period | CALCIUM, TOTAL, high | 0 participants |
| Placebo IV | Number of Participants With Marked Electrolyte Laboratory Abnormalities in the Double Blind Period | PHOSPHORUS, INORGANIC, low | 4 participants |
Secondary
Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period
LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value HEMOGLOBIN g/L 4.0 HB \>3 G/DL DECREASE FROM PRE RX HEMATOCRIT vol 6.3 HCT \<0.75X PRE RX ERYTHROCYTES x10\*12 c/L 5.2 RBC \<0.75X PRE RX PLATELET COUNT x10\*9 c/L 5.0 PLAT \<0.67X LLN OR \>1.5X ULN, OR IF PRE RX\<LLN THEN USE 0.5X PRE RX AND \<100,000/MM3 LEUKOCYTES x10\*9 c/L 6.2 WBC \<0.75X LLN OR \>1.25X ULN, OR IF PRE RX\<LLN THEN USE \<0.8X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.2X PRE RX OR \<LLN EOSINOPHILS (ABSOLUTE) x10\*9 c/L 8.3 EOSA IF VALUE \> .750 X10\*3 c/uL BASOPHILS (ABSOLUTE) x10\*9 c/L 8.3 BASOA IF VALUE \> 400/MM3 MONOCYTES (ABSOLUTE) x10\*9 c/L 8.3 MONOA IF VALUE \> 2000/MM3 LYMPHOCYTES (ABSOLUTE) x10\*9 c/L 8.3 LYMPA IF VALUE \< .750 X10\*3 c/uL OR IF VALUE \> 7.50 X10\*3 c/uL N = the number of participants with at least 1 on treatment lab result for each analyte
Time frame: Day 1 to Day 365; includes data up to 56 days post last dose in year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier
Population: All treated participants~NA (not available) indicates not-calculated as it was not a relevant pre-specified marked abnormality.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | LEUKOCYTES, high | 29 participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | HEMOGLOBIN, high | NA participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | EOSINOPHILS (ABSOLUTE), low | NA participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | ERYTHROCYTES, high | NA participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | EOSINOPHILS (ABSOLUTE), high | 2 participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | HEMOGLOBIN, low | 6 participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | BASOPHILS (ABSOLUTE), low | NA participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | PLATELET COUNT, low | 4 participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | BASOPHILS (ABSOLUTE), high | 1 participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | HEMATOCRIT, low | 12 participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | MONOCYTES (ABSOLUTE), low | NA participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | PLATELET COUNT, high | 0 participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | MONOCYTES (ABSOLUTE), high | 0 participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | HEMATOCRIT, high | NA participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | LYMPHOCYTES (ABSOLUTE), low | 81 participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | LEUKOCYTES, low | 35 participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | LYMPHOCYTES (ABSOLUTE), high | 1 participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | ERYTHROCYTES, low | 7 participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | LYMPHOCYTES (ABSOLUTE), high | 2 participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | HEMOGLOBIN, low | 10 participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | HEMOGLOBIN, high | NA participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | HEMATOCRIT, high | NA participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | ERYTHROCYTES, low | 10 participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | ERYTHROCYTES, high | NA participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | PLATELET COUNT, low | 3 participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | PLATELET COUNT, high | 0 participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | LEUKOCYTES, low | 21 participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | LEUKOCYTES, high | 25 participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | EOSINOPHILS (ABSOLUTE), low | NA participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | EOSINOPHILS (ABSOLUTE), high | 6 participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | BASOPHILS (ABSOLUTE), low | NA participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | BASOPHILS (ABSOLUTE), high | 1 participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | MONOCYTES (ABSOLUTE), low | NA participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | MONOCYTES (ABSOLUTE), high | 1 participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | LYMPHOCYTES (ABSOLUTE), low | 104 participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period | HEMATOCRIT, low | 12 participants |
Secondary
Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period
LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value HEMOGLOBIN g/L 4.0 HB \>3 G/DL DECREASE FROM PRE RX HEMATOCRIT vol 6.3 HCT \<0.75X PRE RX ERYTHROCYTES x10\*12 c/L 5.2 RBC \<0.75X PRE RX PLATELET COUNT x10\*9 c/L 5.0 PLAT \<0.67X LLN OR \>1.5X ULN, OR IF PRE RX\<LLN THEN USE 0.5X PRE RX AND \<100,000/MM3 LEUKOCYTES x10\*9 c/L 6.2 WBC \<0.75X LLN OR \>1.25X ULN, OR IF PRE RX\<LLN THEN USE \<0.8X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.2X PRE RX OR \<LLN EOSINOPHILS (ABSOLUTE) x10\*9 c/L 8.3 EOSA IF VALUE \> .750 X10\*3 c/uL BASOPHILS (ABSOLUTE) x10\*9 c/L 8.3 BASOA IF VALUE \> 400/MM3 MONOCYTES (ABSOLUTE) x10\*9 c/L 8.3 MONOA IF VALUE \> 2000/MM3 LYMPHOCYTES (ABSOLUTE) x10\*9 c/L 8.3 LYMPA IF VALUE \< .750 X10\*3 c/uL OR IF VALUE \> 7.50 X10\*3 c/uL N = the number of participants with at least 1 on treatment lab result for each analyte
Time frame: Day 1 to Day 729
Population: All treated participants~NA (not available) indicates not-calculated as it was not a relevant pre-specified marked abnormality.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | HEMOGLOBIN, low | 8 participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | HEMOGLOBIN, high | NA participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | HEMATOCRIT, low | 6 participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | HEMATOCRIT, high | NA participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | ERYTHROCYTES, low | 4 participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | ERYTHROCYTES, high | NA participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | PLATELET COUNT, low | 2 participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | PLATELET COUNT, high | 1 participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | LEUKOCYTES, low | 19 participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | LEUKOCYTES, high | 3 participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | EOSINOPHILS (ABSOLUTE), low | NA participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | EOSINOPHILS (ABSOLUTE), high | 11 participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | BASOPHILS (ABSOLUTE), low | NA participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | BASOPHILS (ABSOLUTE), high | 0 participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | MONOCYTES (ABSOLUTE), low | NA participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | MONOCYTES (ABSOLUTE), high | 0 participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | LYMPHOCYTES (ABSOLUTE), low | 43 participants |
| Abatacept IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | LYMPHOCYTES (ABSOLUTE), high | 0 participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | BASOPHILS (ABSOLUTE), high | 0 participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | HEMOGLOBIN, low | 9 participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | LEUKOCYTES, high | 5 participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | HEMOGLOBIN, high | NA participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | LYMPHOCYTES (ABSOLUTE), high | 0 participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | HEMATOCRIT, low | 2 participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | EOSINOPHILS (ABSOLUTE), low | NA participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | HEMATOCRIT, high | NA participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | MONOCYTES (ABSOLUTE), low | NA participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | ERYTHROCYTES, low | 2 participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | EOSINOPHILS (ABSOLUTE), high | 6 participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | ERYTHROCYTES, high | NA participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | LYMPHOCYTES (ABSOLUTE), low | 62 participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | PLATELET COUNT, low | 4 participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | BASOPHILS (ABSOLUTE), low | NA participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | PLATELET COUNT, high | 0 participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | MONOCYTES (ABSOLUTE), high | 0 participants |
| Placebo IV | Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period | LEUKOCYTES, low | 24 participants |
Secondary
Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period
LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value ALKALINE PHOSPHATASE (ALP) U/L 5.0 ALP \>2X ULN, OR IF PRE RX\>ULN THEN USE \>3X PRE RX ASPARTATE AMINOTRANSFERASE (AST) U/L 5.0 AST \>3X ULN, OR IF PRE RX\>ULN THEN USE \>4X PRE RX ALANINE AMINOTRANSFERASE (ALT) U/L 5.0 ALT \>3X ULN, OR IF PRE RX\>ULN THEN USE \>4X PRE RX G-GLUTAMYL TRANSFERASE (GGT) U/L 5.0 GGT \>2X ULN, OR IF PRE RX\>ULN THEN USE \>3X PRE RX BILIRUBIN, TOTAL umol/L 5.1 TBILI \>2X ULN, OR IF PRE RX\>ULN THEN USE \>4X PRE RX BILIRUBIN, DIRECT umol/L 5.1 DBILI \>1.5X ULN, OR IF PRE RX\>ULN THEN USE \>2X PRE RX BLOOD UREA NITROGEN mmol/L 5.1 BUN \>2X PRE RX CREATININE umol/L 5.0 CREAT \>1.5X PRE RX N = the number of participants with at least 1 on treatment lab result for each analyte
Time frame: Day 1 to Day 365; includes data up to 56 days post last dose in year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier
Population: All treated participants~NA (not available) indicates not-calculated as it was not a relevant pre-specified marked abnormality.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | BILIRUBIN, TOTAL, high | 0 participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | ALKALINE PHOSPHATASE (ALP), low | NA participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | ALKALINE PHOSPHATASE (ALP), high | 1 participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | ASPARTATE AMINOTRANSFERASE (AST), low | NA participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | ASPARTATE AMINOTRANSFERASE (AST), high | 5 participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | ALANINE AMINOTRANSFERASE (ALT), low | NA participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | ALANINE AMINOTRANSFERASE (ALT), high | 8 participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | G-GLUTAMYL TRANSFERASE (GGT), low | NA participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | G-GLUTAMYL TRANSFERASE (GGT), high | 17 participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | BILIRUBIN, TOTAL, low | NA participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | BILIRUBIN, DIRECT, low | NA participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | BILIRUBIN, DIRECT, high | 0 participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | BLOOD UREA NITROGEN, low | NA participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | BLOOD UREA NITROGEN, high | 20 participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | CREATININE, low | NA participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | CREATININE, high | 24 participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | CREATININE, high | 20 participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | BILIRUBIN, TOTAL, high | 0 participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | G-GLUTAMYL TRANSFERASE (GGT), high | 15 participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | ALKALINE PHOSPHATASE (ALP), low | NA participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | BLOOD UREA NITROGEN, low | NA participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | ALKALINE PHOSPHATASE (ALP), high | 1 participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | BILIRUBIN, TOTAL, low | NA participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | ASPARTATE AMINOTRANSFERASE (AST), low | NA participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | CREATININE, low | NA participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | ASPARTATE AMINOTRANSFERASE (AST), high | 0 participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | BILIRUBIN, DIRECT, low | NA participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | ALANINE AMINOTRANSFERASE (ALT), low | NA participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | BLOOD UREA NITROGEN, high | 12 participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | ALANINE AMINOTRANSFERASE (ALT), high | 2 participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | BILIRUBIN, DIRECT, high | 0 participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period | G-GLUTAMYL TRANSFERASE (GGT), low | NA participants |
Secondary
Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period
LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value ALKALINE PHOSPHATASE (ALP) U/L 5.0 ALP \>2X ULN, OR IF PRE RX\>ULN THEN USE \>3X PRE RX ASPARTATE AMINOTRANSFERASE (AST) U/L 5.0 AST \>3X ULN, OR IF PRE RX\>ULN THEN USE \>4X PRE RX ALANINE AMINOTRANSFERASE (ALT) U/L 5.0 ALT \>3X ULN, OR IF PRE RX\>ULN THEN USE \>4X PRE RX G-GLUTAMYL TRANSFERASE (GGT) U/L 5.0 GGT \>2X ULN, OR IF PRE RX\>ULN THEN USE \>3X PRE RX BILIRUBIN, TOTAL umol/L 5.1 TBILI \>2X ULN, OR IF PRE RX\>ULN THEN USE \>4X PRE RX BILIRUBIN, DIRECT umol/L 5.1 DBILI \>1.5X ULN, OR IF PRE RX\>ULN THEN USE \>2X PRE RX BLOOD UREA NITROGEN mmol/L 5.1 BUN \>2X PRE RX CREATININE umol/L 5.0 CREAT \>1.5X PRE RX N = the number of participants with at least 1 on treatment lab result for each analyte
Time frame: Day 1 to Day 729
Population: All treated participants~NA (not available) indicates not-calculated as it was not a relevant pre-specified marked abnormality.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | ASPARTATE AMINOTRANSFERASE (AST), low | NA participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | BILIRUBIN, TOTAL, low | NA participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | ASPARTATE AMINOTRANSFERASE (AST), high | 2 participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | BILIRUBIN, TOTAL, high | 0 participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | ALANINE AMINOTRANSFERASE (ALT), low | NA participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | BILIRUBIN, DIRECT, low | NA participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | CREATININE, low | NA participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | BILIRUBIN, DIRECT, high | 1 participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | ALANINE AMINOTRANSFERASE (ALT), high | 4 participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | BLOOD UREA NITROGEN, low | NA participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | ALKALINE PHOSPHATASE (ALP), high | 4 participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | BLOOD UREA NITROGEN, high | 10 participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | G-GLUTAMYL TRANSFERASE (GGT), low | NA participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | ALKALINE PHOSPHATASE (ALP), low | NA participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | CREATININE, high | 17 participants |
| Abatacept IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | G-GLUTAMYL TRANSFERASE (GGT), high | 17 participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | CREATININE, high | 16 participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | ASPARTATE AMINOTRANSFERASE (AST), high | 3 participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | ALKALINE PHOSPHATASE (ALP), low | NA participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | ALKALINE PHOSPHATASE (ALP), high | 0 participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | ALANINE AMINOTRANSFERASE (ALT), low | NA participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | ALANINE AMINOTRANSFERASE (ALT), high | 3 participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | G-GLUTAMYL TRANSFERASE (GGT), low | NA participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | G-GLUTAMYL TRANSFERASE (GGT), high | 11 participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | BILIRUBIN, TOTAL, low | NA participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | BILIRUBIN, TOTAL, high | 0 participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | BILIRUBIN, DIRECT, low | NA participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | BILIRUBIN, DIRECT, high | 0 participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | BLOOD UREA NITROGEN, low | NA participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | BLOOD UREA NITROGEN, high | 9 participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | CREATININE, low | NA participants |
| Placebo IV | Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period | ASPARTATE AMINOTRANSFERASE (AST), low | NA participants |
Secondary
Number of Participants With Marked Urinalysis Laboratory Abnormalities During Year 1 of the Double Blind Period
LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value PROTEIN, URINE Unknown UPRO IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4 GLUCOSE, URINE N/A UGLU IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4 BLOOD, URINE N/A UBLD IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4 RBC, URINE hpf 5.0 URBC IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4 WBC, URINE hpf 5.0 UWBC IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4
Time frame: Day 1 to Day 365; includes data up to 56 days post last dose in year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier
Population: All treated participants~N = the number of participants with at least 1 on treatment lab result for each analyte~NA (not available) indicates not-calculated as it was not a relevant pre-specified marked abnormality.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities During Year 1 of the Double Blind Period | GLUCOSE, URINE, high | 0 participants |
| Abatacept IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities During Year 1 of the Double Blind Period | PROTEIN, URINE, low | NA participants |
| Abatacept IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities During Year 1 of the Double Blind Period | PROTEIN, URINE, high | 0 participants |
| Abatacept IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities During Year 1 of the Double Blind Period | GLUCOSE, URINE, low | NA participants |
| Abatacept IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities During Year 1 of the Double Blind Period | BLOOD, URINE, low | NA participants |
| Abatacept IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities During Year 1 of the Double Blind Period | BLOOD, URINE, high | 0 participants |
| Abatacept IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities During Year 1 of the Double Blind Period | Red blood cells (RBC), URINE, low | NA participants |
| Abatacept IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities During Year 1 of the Double Blind Period | Red blood cells (RBC), URINE, high | 93 participants |
| Abatacept IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities During Year 1 of the Double Blind Period | White blood cells (WBC), URINE, low | NA participants |
| Abatacept IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities During Year 1 of the Double Blind Period | White blood cells (WBC), URINE, high | 91 participants |
| Placebo IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities During Year 1 of the Double Blind Period | Red blood cells (RBC), URINE, high | 103 participants |
| Placebo IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities During Year 1 of the Double Blind Period | BLOOD, URINE, high | 0 participants |
| Placebo IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities During Year 1 of the Double Blind Period | PROTEIN, URINE, low | NA participants |
| Placebo IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities During Year 1 of the Double Blind Period | White blood cells (WBC), URINE, high | 98 participants |
| Placebo IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities During Year 1 of the Double Blind Period | PROTEIN, URINE, high | 0 participants |
| Placebo IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities During Year 1 of the Double Blind Period | Red blood cells (RBC), URINE, low | NA participants |
| Placebo IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities During Year 1 of the Double Blind Period | GLUCOSE, URINE, low | NA participants |
| Placebo IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities During Year 1 of the Double Blind Period | GLUCOSE, URINE, high | 0 participants |
| Placebo IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities During Year 1 of the Double Blind Period | White blood cells (WBC), URINE, low | NA participants |
| Placebo IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities During Year 1 of the Double Blind Period | BLOOD, URINE, low | NA participants |
Secondary
Number of Participants With Marked Urinalysis Laboratory Abnormalities in the Double Blind Period
LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value PROTEIN, URINE Unknown UPRO IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4 GLUCOSE, URINE N/A UGLU IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4 BLOOD, URINE N/A UBLD IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4 RBC, URINE hpf 5.0 URBC IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4 WBC, URINE hpf 5.0 UWBC IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4
Time frame: Day 1 to Day 729
Population: All treated participants~N = the number of participants with at least 1 on treatment lab result for each analyte~NA (not available) indicates not-calculated as it was not a relevant pre-specified marked abnormality.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities in the Double Blind Period | White blood cells (WBC), URINE, high | 46 participants |
| Abatacept IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities in the Double Blind Period | Red blood cells (RBC), URINE, low | NA participants |
| Abatacept IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities in the Double Blind Period | PROTEIN, URINE, low | NA participants |
| Abatacept IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities in the Double Blind Period | GLUCOSE, URINE, low | NA participants |
| Abatacept IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities in the Double Blind Period | GLUCOSE, URINE, high | 0 participants |
| Abatacept IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities in the Double Blind Period | BLOOD, URINE, low | NA participants |
| Abatacept IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities in the Double Blind Period | BLOOD, URINE, high | 0 participants |
| Abatacept IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities in the Double Blind Period | Red blood cells (RBC), URINE, high | 58 participants |
| Abatacept IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities in the Double Blind Period | White blood cells (WBC), URINE, low | NA participants |
| Abatacept IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities in the Double Blind Period | PROTEIN, URINE, high | 0 participants |
| Placebo IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities in the Double Blind Period | BLOOD, URINE, high | 0 participants |
| Placebo IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities in the Double Blind Period | BLOOD, URINE, low | NA participants |
| Placebo IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities in the Double Blind Period | GLUCOSE, URINE, high | 0 participants |
| Placebo IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities in the Double Blind Period | White blood cells (WBC), URINE, low | NA participants |
| Placebo IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities in the Double Blind Period | White blood cells (WBC), URINE, high | 59 participants |
| Placebo IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities in the Double Blind Period | Red blood cells (RBC), URINE, low | NA participants |
| Placebo IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities in the Double Blind Period | PROTEIN, URINE, low | NA participants |
| Placebo IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities in the Double Blind Period | PROTEIN, URINE, high | 0 participants |
| Placebo IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities in the Double Blind Period | Red blood cells (RBC), URINE, high | 55 participants |
| Placebo IV | Number of Participants With Marked Urinalysis Laboratory Abnormalities in the Double Blind Period | GLUCOSE, URINE, low | NA participants |
Secondary
Number of Participants With Other Marked Chemistry Laboratory Abnormalities During Year 1 of the Double Blind Period
LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value CALCIUM, TOTAL mmol/L 5.2 CA \<0.8X LLN OR \>1.2X ULN, OR IF PRE RX\<LLN THEN USE \<0.75X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.25X PRE RX OR \<LLN PHOSPHORUS, INORGANIC mmol/L 5.2 PHOS \<0.75X LLN OR \>1.25X ULN, OR IF PRE RX\<LLN THEN USE \<0.67X PRE RX OR \>ULN GLUCOSE, SERUM mmol/L 4.1 GLUC \<65 mg/dL, OR \>220 mg/dL PROTEIN, TOTAL g/L 5.0 TPRO \<0.9X LLN OR \>1.1X ULN, OR IF PRE RX\<LLN THEN USE 0.9X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE 1.1X PRE RX OR \<LLN ALBUMIN g/L 3.0 ALB \<0.9X LLN, OR IF PRE RX\<LLN THEN USE \<0.75X PRE RX CHOLESTEROL, TOTAL (TC) mmol/L 5.2 CHOL \>2X PRE R N = the number of participants with at least 1 on treatment lab result for each analyte
Time frame: Day 1 to Day 365; includes data up to 56 days post last dose in year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier
Population: All treated participants~NA (not available) indicates not-calculated as it was not a relevant pre-specified marked abnormality.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept IV | Number of Participants With Other Marked Chemistry Laboratory Abnormalities During Year 1 of the Double Blind Period | GLUCOSE, SERUM, low | 33 participants |
| Abatacept IV | Number of Participants With Other Marked Chemistry Laboratory Abnormalities During Year 1 of the Double Blind Period | GLUCOSE, SERUM, high | 10 participants |
| Abatacept IV | Number of Participants With Other Marked Chemistry Laboratory Abnormalities During Year 1 of the Double Blind Period | PROTEIN, TOTAL, low | 44 participants |
| Abatacept IV | Number of Participants With Other Marked Chemistry Laboratory Abnormalities During Year 1 of the Double Blind Period | PROTEIN, TOTAL, high | 0 participants |
| Abatacept IV | Number of Participants With Other Marked Chemistry Laboratory Abnormalities During Year 1 of the Double Blind Period | ALBUMIN, low | 10 participants |
| Abatacept IV | Number of Participants With Other Marked Chemistry Laboratory Abnormalities During Year 1 of the Double Blind Period | ALBUMIN, high | NA participants |
| Placebo IV | Number of Participants With Other Marked Chemistry Laboratory Abnormalities During Year 1 of the Double Blind Period | ALBUMIN, low | 11 participants |
| Placebo IV | Number of Participants With Other Marked Chemistry Laboratory Abnormalities During Year 1 of the Double Blind Period | GLUCOSE, SERUM, low | 29 participants |
| Placebo IV | Number of Participants With Other Marked Chemistry Laboratory Abnormalities During Year 1 of the Double Blind Period | PROTEIN, TOTAL, high | 1 participants |
| Placebo IV | Number of Participants With Other Marked Chemistry Laboratory Abnormalities During Year 1 of the Double Blind Period | GLUCOSE, SERUM, high | 5 participants |
| Placebo IV | Number of Participants With Other Marked Chemistry Laboratory Abnormalities During Year 1 of the Double Blind Period | ALBUMIN, high | NA participants |
| Placebo IV | Number of Participants With Other Marked Chemistry Laboratory Abnormalities During Year 1 of the Double Blind Period | PROTEIN, TOTAL, low | 26 participants |
Secondary
Number of Participants With Other Marked Chemistry Laboratory Abnormalities in the Double Blind Period
LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value CALCIUM, TOTAL mmol/L 5.2 CA \<0.8X LLN OR \>1.2X ULN, OR IF PRE RX\<LLN THEN USE \<0.75X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.25X PRE RX OR \<LLN PHOSPHORUS, INORGANIC mmol/L 5.2 PHOS \<0.75X LLN OR \>1.25X ULN, OR IF PRE RX\<LLN THEN USE \<0.67X PRE RX OR \>ULN GLUCOSE, SERUM mmol/L 4.1 GLUC \<65 mg/dL, OR \>220 mg/dL PROTEIN, TOTAL g/L 5.0 TPRO \<0.9X LLN OR \>1.1X ULN, OR IF PRE RX\<LLN THEN USE 0.9X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE 1.1X PRE RX OR \<LLN ALBUMIN g/L 3.0 ALB \<0.9X LLN, OR IF PRE RX\<LLN THEN USE \<0.75X PRE RX CHOLESTEROL, TOTAL (TC) mmol/L 5.2 CHOL \>2X PRE R N = the number of participants with at least 1 on treatment lab result for each analyte
Time frame: Day 1 to Day 729
Population: All treated participants~NA (not available) indicates not-calculated as it was not a relevant pre-specified marked abnormality.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept IV | Number of Participants With Other Marked Chemistry Laboratory Abnormalities in the Double Blind Period | PROTEIN, TOTAL, low | 10 participants |
| Abatacept IV | Number of Participants With Other Marked Chemistry Laboratory Abnormalities in the Double Blind Period | GLUCOSE, SERUM, low | 15 participants |
| Abatacept IV | Number of Participants With Other Marked Chemistry Laboratory Abnormalities in the Double Blind Period | PROTEIN, TOTAL, high | 2 participants |
| Abatacept IV | Number of Participants With Other Marked Chemistry Laboratory Abnormalities in the Double Blind Period | GLUCOSE, FASTING SERUM, low | 3 participants |
| Abatacept IV | Number of Participants With Other Marked Chemistry Laboratory Abnormalities in the Double Blind Period | ALBUMIN, low | 4 participants |
| Abatacept IV | Number of Participants With Other Marked Chemistry Laboratory Abnormalities in the Double Blind Period | GLUCOSE, FASTING SERUM, high | 3 participants |
| Abatacept IV | Number of Participants With Other Marked Chemistry Laboratory Abnormalities in the Double Blind Period | ALBUMIN, high | NA participants |
| Abatacept IV | Number of Participants With Other Marked Chemistry Laboratory Abnormalities in the Double Blind Period | GLUCOSE, SERUM, high | 3 participants |
| Placebo IV | Number of Participants With Other Marked Chemistry Laboratory Abnormalities in the Double Blind Period | ALBUMIN, high | NA participants |
| Placebo IV | Number of Participants With Other Marked Chemistry Laboratory Abnormalities in the Double Blind Period | GLUCOSE, SERUM, low | 24 participants |
| Placebo IV | Number of Participants With Other Marked Chemistry Laboratory Abnormalities in the Double Blind Period | GLUCOSE, SERUM, high | 2 participants |
| Placebo IV | Number of Participants With Other Marked Chemistry Laboratory Abnormalities in the Double Blind Period | GLUCOSE, FASTING SERUM, high | 1 participants |
| Placebo IV | Number of Participants With Other Marked Chemistry Laboratory Abnormalities in the Double Blind Period | PROTEIN, TOTAL, low | 7 participants |
| Placebo IV | Number of Participants With Other Marked Chemistry Laboratory Abnormalities in the Double Blind Period | PROTEIN, TOTAL, high | 3 participants |
| Placebo IV | Number of Participants With Other Marked Chemistry Laboratory Abnormalities in the Double Blind Period | ALBUMIN, low | 5 participants |
| Placebo IV | Number of Participants With Other Marked Chemistry Laboratory Abnormalities in the Double Blind Period | GLUCOSE, FASTING SERUM, low | 1 participants |
Secondary
Number of Participants With Sustained Change From Higher Level of Response to no Response During the Double-blind Period
Sustained change to no response is defined as going from CR (or PR) to NR and remaining in NR for at least 2 consecutive visits; visits should be approximately 4 weeks apart. This analysis will be based on time from response CR (or PR) to the first visit in which the no response (NR) was achieved and sustained to the next visit.
Time frame: Day 365, Day 729
Population: All randomized and treated participants, as observed, calculated per modified criteria (UPCR and eGFR only)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept IV | Number of Participants With Sustained Change From Higher Level of Response to no Response During the Double-blind Period | Day 365 | 5 Participants |
| Abatacept IV | Number of Participants With Sustained Change From Higher Level of Response to no Response During the Double-blind Period | Day 729 | 52 Participants |
| Placebo IV | Number of Participants With Sustained Change From Higher Level of Response to no Response During the Double-blind Period | Day 365 | 3 Participants |
| Placebo IV | Number of Participants With Sustained Change From Higher Level of Response to no Response During the Double-blind Period | Day 729 | 56 Participants |
95% CI: [0.3251, 6.2849]
95% CI: [-8.4, 15.1]
Secondary
Percentage of Nephrotic Participants in Complete Renal Response of Lupus Glomerulonephritis at Day 365 of the Double-blind Period
Number of participants achieving CR was divided by total participants in that arm, expressed as a percentage. CR is defined the following criteria: eGFR is normal or no \<85% of the baseline value; eGFR is based on mean creatinine value from day 358 and 365. Proteinuria: UPCR\<0.5 mg/mg. Urine sediment: No cellular casts. Corticosteroid dose: Daily dose must be no \>10 mg prednisone or equivalent for at least 28 days prior. Subjects with \>10mg/day prednisone or equivalent for non-renal disease within 28 days prior to day 365 will be imputed as CR if the following are true: Met all criteria for CR at day 337 and all criteria for CR except corticosteroid dose at day 365; Investigator confirms increase in steroid dose is not related to renal disease. Adjusted odds ratio is estimated from logistic regression model which includes treatment group, baseline ACEi/ARBs use, race and baseline UPCR as a continuous variable.
Time frame: Day 365
Population: All randomized and treated nephrotic participants. Nephrotic is defined as screening UPCR \>= 3.0mg/mg (\>=339mg/mmol)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abatacept IV | Percentage of Nephrotic Participants in Complete Renal Response of Lupus Glomerulonephritis at Day 365 of the Double-blind Period | 27 Percentage |
| Placebo IV | Percentage of Nephrotic Participants in Complete Renal Response of Lupus Glomerulonephritis at Day 365 of the Double-blind Period | 29.5 Percentage |
95% CI: [0.4148, 1.5956]
Secondary
Percentage of Nephrotic Participants in Complete Renal Response of Lupus Glomerulonephritis at Day 729 of the Double-blind Period
Number of participants achieving CR was divided by total participants in that arm, expressed as a percentage. CR is defined the following criteria: eGFR is normal or no \<85% of the baseline value; eGFR is based on mean creatinine value from day 358 and 365. Proteinuria: UPCR\<0.5 mg/mg. Urine sediment: No cellular casts. Corticosteroid dose: Daily dose must be no \>10 mg prednisone or equivalent for at least 28 days prior. Subjects with \>10mg/day prednisone or equivalent for non-renal disease within 28 days prior to day 365 will be imputed as CR if the following are true: Met all criteria for CR at day 337 and all criteria for CR except corticosteroid dose at day 365; Investigator confirms increase in steroid dose is not related to renal disease. Adjusted odds ratio is estimated from logistic regression model which includes treatment group, baseline ACEi/ARBs use, race and baseline UPCR as a continuous variable.
Time frame: Day 729
Population: All randomized and treated nephrotic participants, as observed, calculated per modified criteria (UPCR and eGFR only). Nephrotic is defined as screening UPCR \>= 3.0mg/mg (\>=339mg/mmol)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abatacept IV | Percentage of Nephrotic Participants in Complete Renal Response of Lupus Glomerulonephritis at Day 729 of the Double-blind Period | 50.0 Percentage |
| Placebo IV | Percentage of Nephrotic Participants in Complete Renal Response of Lupus Glomerulonephritis at Day 729 of the Double-blind Period | 49.0 Percentage |
Secondary
Percentage of Participants in Overall Population in Complete Renal Response of Lupus Glomerulonephritis at Day 729 of the Double-blind Period
Number of participants achieving CR was divided by total participants in that arm, expressed as a percentage. CR is defined the following criteria: eGFR is normal or no \<85% of the baseline value; eGFR is based on mean creatinine value from day 358 and 365. Proteinuria: UPCR\<0.5 mg/mg. Urine sediment: No cellular casts. Corticosteroid dose: Daily dose must be no \>10 mg prednisone or equivalent for at least 28 days prior. Subjects with \>10mg/day prednisone or equivalent for non-renal disease within 28 days prior to day 365 will be imputed as CR if the following are true: Met all criteria for CR at day 337 and all criteria for CR except corticosteroid dose at day 365; Investigator confirms increase in steroid dose is not related to renal disease. Adjusted odds ratio is estimated from logistic regression model which includes treatment group, baseline ACEi/ARBs use, race and baseline UPCR as a continuous variable.
Time frame: Day 729
Population: All randomized and treated participants, as observed, calculated per modified criteria (UPCR and eGFR only)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abatacept IV | Percentage of Participants in Overall Population in Complete Renal Response of Lupus Glomerulonephritis at Day 729 of the Double-blind Period | 61.9 Percentage |
| Placebo IV | Percentage of Participants in Overall Population in Complete Renal Response of Lupus Glomerulonephritis at Day 729 of the Double-blind Period | 52.7 Percentage |
Secondary
Percentage of Participants in Treatment Failure Over Time During the Double-blind Period
Lupus treatment failure is defined as any of the following: Death, unless due to physical trauma or violence; Renal Flare; sustained doubling of creatinine from baseline (greater of Screening or Study Day 1 value); initiation of rescue therapy for treatment of active lupus nephritis after Study Week 20. Overall treatment failure is defined as lupus treatment failure plus discontinuation of study drug for any reason except death due to physical trauma or violence, pregnancy or administrative decision by Sponsor.
Time frame: Day 365, Day 729
Population: All randomized and treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept IV | Percentage of Participants in Treatment Failure Over Time During the Double-blind Period | Lupus treatment failure (LTF) - Day 365 | 3.5 Percentage |
| Abatacept IV | Percentage of Participants in Treatment Failure Over Time During the Double-blind Period | LTF - Day 729 | 4.5 Percentage |
| Abatacept IV | Percentage of Participants in Treatment Failure Over Time During the Double-blind Period | Overall treatment failure (OTF) - Day 365 | 4.5 Percentage |
| Abatacept IV | Percentage of Participants in Treatment Failure Over Time During the Double-blind Period | OTF - Day 729 | 5.2 Percentage |
| Placebo IV | Percentage of Participants in Treatment Failure Over Time During the Double-blind Period | Overall treatment failure (OTF) - Day 365 | 4.9 Percentage |
| Placebo IV | Percentage of Participants in Treatment Failure Over Time During the Double-blind Period | Lupus treatment failure (LTF) - Day 365 | 4.4 Percentage |
| Placebo IV | Percentage of Participants in Treatment Failure Over Time During the Double-blind Period | OTF - Day 729 | 8.4 Percentage |
| Placebo IV | Percentage of Participants in Treatment Failure Over Time During the Double-blind Period | LTF - Day 729 | 5.3 Percentage |
Comparison: Lupus treatment failure - Day 36595% CI: [-4.760178, 2.823876]
Comparison: Overall treatment failure - Day 36595% CI: [-4.588691, 3.647365]
95% CI: [-4.5, 6.1]
95% CI: [-3.3, 8.8]
Secondary
Percentage of Participants With Ranked Outcome of Complete Renal Response, Partial Renal Response (PR), and No Renal Response (NR) During the Double-blind Period
Complete Renal Response or Complete Response (CR): defined as meeting ALL of the following criteria: eGFR normal OR no less than 85% of the baseline value; UPCR \< 0.5; Urine sediment: No cellular casts; Daily corticosteroid dose must be no greater than 10 mg prednisone or equivalent for at least 28 days prior to assessment. Partial Renal Response or Partial Response (PR): defined as meeting ALL of the following criteria: Participant does not meet criteria for CR; eGFR no less than 85% of the lesser of the values at screening or randomization (Day 1); UPCR \< 0.5 OR 50% reduced from baseline and \< 1 if baseline value was \< 3, OR 50% reduced from baseline and \< 3 if baseline value was greater than or equal to 3; Urine sediment: no cellular casts; daily corticosteroid dose no greater than 10 mg/day prednisone or prednisone equivalent for at least 28 days prior to assessment. No Renal Response or No Response (NR): defined as not meeting criteria for CR or PR or withdrawn
Time frame: Day 365, Day 729
Population: All randomized and treated participants.~Year 1 data based on all elements of clinical response definition: UPCR, eGFR and cellular casts.~Study terminated and Year 2 data based on only two clinical response definition elements: UPCR and eGFR. Data presented for the as observed population (those that completed Day 729).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept IV | Percentage of Participants With Ranked Outcome of Complete Renal Response, Partial Renal Response (PR), and No Renal Response (NR) During the Double-blind Period | CR - Day 365 | 35.1 Percentage |
| Abatacept IV | Percentage of Participants With Ranked Outcome of Complete Renal Response, Partial Renal Response (PR), and No Renal Response (NR) During the Double-blind Period | PR - Day 365 | 20.8 Percentage |
| Abatacept IV | Percentage of Participants With Ranked Outcome of Complete Renal Response, Partial Renal Response (PR), and No Renal Response (NR) During the Double-blind Period | NR - Day 365 | 44.1 Percentage |
| Abatacept IV | Percentage of Participants With Ranked Outcome of Complete Renal Response, Partial Renal Response (PR), and No Renal Response (NR) During the Double-blind Period | CR - Day 729 | 60.7 Percentage |
| Abatacept IV | Percentage of Participants With Ranked Outcome of Complete Renal Response, Partial Renal Response (PR), and No Renal Response (NR) During the Double-blind Period | PR - Day 729 | 25.9 Percentage |
| Abatacept IV | Percentage of Participants With Ranked Outcome of Complete Renal Response, Partial Renal Response (PR), and No Renal Response (NR) During the Double-blind Period | NR - Day 729 | 13.4 Percentage |
| Placebo IV | Percentage of Participants With Ranked Outcome of Complete Renal Response, Partial Renal Response (PR), and No Renal Response (NR) During the Double-blind Period | PR - Day 729 | 22.7 Percentage |
| Placebo IV | Percentage of Participants With Ranked Outcome of Complete Renal Response, Partial Renal Response (PR), and No Renal Response (NR) During the Double-blind Period | CR - Day 365 | 33.5 Percentage |
| Placebo IV | Percentage of Participants With Ranked Outcome of Complete Renal Response, Partial Renal Response (PR), and No Renal Response (NR) During the Double-blind Period | CR - Day 729 | 53.6 Percentage |
| Placebo IV | Percentage of Participants With Ranked Outcome of Complete Renal Response, Partial Renal Response (PR), and No Renal Response (NR) During the Double-blind Period | PR - Day 365 | 21.7 Percentage |
| Placebo IV | Percentage of Participants With Ranked Outcome of Complete Renal Response, Partial Renal Response (PR), and No Renal Response (NR) During the Double-blind Period | NR - Day 729 | 23.6 Percentage |
| Placebo IV | Percentage of Participants With Ranked Outcome of Complete Renal Response, Partial Renal Response (PR), and No Renal Response (NR) During the Double-blind Period | NR - Day 365 | 44.8 Percentage |
Comparison: CR - Day 36595% CI: [-7.595828, 10.897784]
Comparison: PR - Day 36595% CI: [-8.848056, 7.082461]
Comparison: NR - Day 36595% CI: [-10.446714, 8.910353]
Secondary
Summary Statistics for Diastolic Blood Pressure
Summary statistics for diastolic blood pressure
Time frame: Day 1 to Day 729
Population: All treated participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept IV | Summary Statistics for Diastolic Blood Pressure | Day 729, end of observation | 67.5 mmHg | Standard Deviation 9.6 |
| Abatacept IV | Summary Statistics for Diastolic Blood Pressure | Day 1, end of observation | 76.5 mmHg | Standard Deviation 11.49 |
| Abatacept IV | Summary Statistics for Diastolic Blood Pressure | Day 365, end of observation | 73.5 mmHg | Standard Deviation 10.75 |
| Placebo IV | Summary Statistics for Diastolic Blood Pressure | Day 1, end of observation | 77.0 mmHg | Standard Deviation 11.19 |
| Placebo IV | Summary Statistics for Diastolic Blood Pressure | Day 365, end of observation | 77.5 mmHg | Standard Deviation 10.61 |
| Placebo IV | Summary Statistics for Diastolic Blood Pressure | Day 729, end of observation | 72.7 mmHg | Standard Deviation 9.45 |
Secondary
Summary Statistics for Heart Rate
Summary statistics for Heart Rate
Time frame: Day 1 to Day 729
Population: All treated participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept IV | Summary Statistics for Heart Rate | Day 1, end of observation | 80.6 beats per minute | Standard Deviation 10.91 |
| Abatacept IV | Summary Statistics for Heart Rate | Day 365, end of observation | 78.5 beats per minute | Standard Deviation 9.57 |
| Abatacept IV | Summary Statistics for Heart Rate | Day 729, end of observation | 76.2 beats per minute | Standard Deviation 11.69 |
| Placebo IV | Summary Statistics for Heart Rate | Day 1, end of observation | 81.4 beats per minute | Standard Deviation 10.64 |
| Placebo IV | Summary Statistics for Heart Rate | Day 365, end of observation | 70.0 beats per minute | Standard Deviation 14.14 |
| Placebo IV | Summary Statistics for Heart Rate | Day 729, end of observation | 76.7 beats per minute | Standard Deviation 10.36 |
Secondary
Summary Statistics for Systolic Blood Pressure
Summary statistics for systolic blood pressure
Time frame: Day 1 to Day 729
Population: All treated participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept IV | Summary Statistics for Systolic Blood Pressure | Day 1, end of observation | 122.0 mmHg | Standard Deviation 15.48 |
| Abatacept IV | Summary Statistics for Systolic Blood Pressure | Day 365, end of observation | 112.3 mmHg | Standard Deviation 18.45 |
| Abatacept IV | Summary Statistics for Systolic Blood Pressure | Day 729, end of observation | 108.6 mmHg | Standard Deviation 13.29 |
| Placebo IV | Summary Statistics for Systolic Blood Pressure | Day 1, end of observation | 122.6 mmHg | Standard Deviation 15.31 |
| Placebo IV | Summary Statistics for Systolic Blood Pressure | Day 365, end of observation | 115.0 mmHg | Standard Deviation 7.07 |
| Placebo IV | Summary Statistics for Systolic Blood Pressure | Day 729, end of observation | 114.2 mmHg | Standard Deviation 14.51 |